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  • 1
    Electronic Resource
    Electronic Resource
    Glycated low density lipoprotein catabolism is increased in rabbits with alloxan-induced diabetes mellitus (1992)
    Springer
    Diabetologia 35 (1992), S. 202-207 
    Details
    ISSN: 1432-0428
    Keywords: Atherosclerosis ; diabetes mellitus ; glycation ; LDL metabolism ; kinetics ; experimental
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyperglycaemia in diabetes mellitus is responsible for the process of non-enzymatic glycosylation of different proteins. Since we did not find elevated glycated apolipoprotein B levels in diabetic patients, an altered glycated apolipoprotein B metabolism was suspected in diabetic patients. Experiments in normal rabbits showed that non-reductive (in vitro) glycated low density lipoprotein (gly-LDL) was cleared at a slower rate than control LDL and thus stayed longer in the circulation (vascular mean residence time: 10 vs 8 h, p〈0.001). The body mean residence time for gly-LDL was 22 h vs 17 h for control LDL. In diabetic animals the catabolic parameters of both LDL preparations changed towards a faster clearance, the effect being greatest for gly-LDL (total mean residence times of gly-LDL pre-diabetic: 19 h, diabetic: 16 h; control LDL pre-diabetic and diabetic: 14 h). The difference in clearance between glycated and control LDL was thus strongly reduced. Virtually no antibody complexed to gly-LDL could be measured. The results suggest an increased activity of the non-receptor mediated pathway in diabetes mellitus, possibly co-responsible for an increased atherosclerotic risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400918
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  • 2
    Electronic Resource
    Electronic Resource
    Randomized double-blind placebo-controlled trial to evaluate the effect of the ACTH4–9 analogue ORG 2766 in IDDM patients with neuropathy (1994)
    Springer
    Diabetologia 37 (1994), S. 408-413 
    Details
    ISSN: 1432-0428
    Keywords: ACTH4–9 analogue ; diabetic neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study we report a randomized double-blind, placebo-controlled trial to evaluate the effect of ORG 2766 in IDDM patients with peripheral neuropathy. Sixty-two patients were selected based on the following criteria: abnormal vibration perception threshold above the 95th-percentile adjusted for age and/or abnormal warm temperature threshold, both measured in the right hand. The patients were randomized into two treatment groups after baseline studies: Group 1 was treated with placebo and Group 2 was treated with 3 mg of the ACTH4–9 analogue ORG 2766 every 24 h. The total study period was 1 year. After 1 year of treatment there was a significant improvement in vibration threshold in Group 1 compared to Group 2. No other parameters improved in the study period. The number of patients selected may have been too small to detect a more important treatment effect. We conclude from this study that ORG 2766 can improve vibration threshold, indicating large myelinated fibre function, but does not affect any the other neurophysiological function tests.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408479
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  • 3
    Electronic Resource
    Electronic Resource
    Cerebral function in diabetes mellitus (1994)
    Springer
    Diabetologia 37 (1994), S. 643-650 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; complications ; brain ; cerebral dysfunction ; cognitive dysfunction ; pathogenesis ; cerebral blood flow ; hypoglycaemia ; hyperglycaemia ; review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetes mellitus is a common metabolic disorder associated with chronic complications such as nephropathy, angiopathy, retinopathy and peripheral neuropathy. Diabetes is not often considered to have deleterious effects on the brain. However, long-term diabetes results in a variety of subtle cerebral disorders, which occur more frequently than is commonly believed. Diabetic cerebral disorders have been demonstrated at a neurochemical, electrophysiological, structural and cognitive level; however, the pathogenesis is still not clear. Probably alterations in cerebral blood supply and metabolic derangements play a role, as they do in the pathogenesis of diabetic neuropathy. Furthermore, the brain is also affected by recurrent episodes of hypoglycaemia and poor metabolic control. We describe herein the cerebral manifestations of diabetes and discuss the putative pathogenetic mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00417687
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  • 4
    Electronic Resource
    Electronic Resource
    Cerebral function in diabetes mellitus (1994)
    Springer
    Diabetologia 37 (1994), S. 643-650 
    Details
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus, complications, brain, cerebral dysfunction, cognitive dysfunction, pathogenesis, cerebral blood flow, hypoglycaemia, hyperglycaemia, review.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetes mellitus is a common metabolic disorder associated with chronic complications such as nephropathy, angiopathy, retinopathy and peripheral neuropathy. Diabetes is not often considered to have deleterious effects on the brain. However, long-term diabetes results in a variety of subtle cerebral disorders, which occur more frequently than is commonly believed. Diabetic cerebral disorders have been demonstrated at a neurochemical, electrophysiological, structural and cognitive level; however, the pathogenesis is still not clear. Probably alterations in cerebral blood supply and metabolic derangements play a role, as they do in the pathogenesis of diabetic neuropathy. Furthermore, the brain is also affected by recurrent episodes of hypoglycaemia and poor metabolic control. We describe herein the cerebral manifestations of diabetes and discuss the putative pathogenetic mechanisms. [Diabetologia (1994) 37: 643–650]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00417687
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  • 5
    Electronic Resource
    Electronic Resource
    Increased cholesterylester transfer activity in complicated Type 1 (insulin-dependent) diabetes mellitus — its relationship with serum lipids (1989)
    Springer
    Diabetologia 32 (1989), S. 14-19 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; cholesterol metabolism ; cholesterylester transfer activity ; microangiopathy ; atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In Type 1 (insulin-dependent) diabetes mellitus, macrovascular complications and the increased risk for cardiovascular disease in patients with microvascular complications may be related to alterations in plasma cholesterylester transfer. The activity of cholesterylester transfer protein, which mediates cholesterylester transfer between lipoproteins and lipoprotein lipid levels, was assessed in 7 normolipidaemic control subjects, 7 Type 1 diabetic control subjects without complications, 11 Type 1 diabetic patients with microvascular complications (retinopathy, incipient nephropathy) and in 7 Type 1 diabetic patients with macrovascular atherosclerotic lesions. The cholesterylester transfer activity was 30% higher in the diabetic groups with macrovascular and microvascular lesions than in the 2 control groups. Very low + low density lipoprotein cholesterol was higher in the 3 diabetic groups than in the non-diabetic control group. High density lipoprotein cholesterol was not different. The cholesterylester transfer activity was correlated positively with HbA1, urinary albumin excretion rate, serum cholesterol, very low + low density lipoprotein cholesterol and apolipoprotein B. The high density lipoprotein over very low + low density lipoprotein cholesterylester molar ratio was lower in the diabetic groups with micro- and macrovascular complications. A role for cholesterylester transfer activity in the lipoprotein abnormalities found in complicated Type 1 diabetes is suggested. A high cholesterylester transfer activity might be indicative of mechanisms which promote atherogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265398
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  • 6
    Electronic Resource
    Electronic Resource
    Potential use of glutathione for the prevention and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat (1992)
    Springer
    Diabetologia 35 (1992), S. 813-817 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; diabetic neuropathy ; oxidative stress ; glutathione ; nerve conduction velocity ; streptozotocin rat model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been shown that parameters of oxidative stress are increased in experimental diabetic neuropathy. The glutathione redox system is one of the intracellular scavenger systems for neutralizing free oxygen radicals. In this investigation we studied the effect of glutathione-treatment on the development of diabetic neuropathy in streptozotocin-induced diabetic rats by measuring sensory and motor nerve conduction velocities. The total study period was 10 weeks. Four groups of rats were studied: Group 1 consisted of non-diabetic, age-matched control rats; Group 2, of diabetic rats treated with placebo from week 0 to 10; Group 3, of diabetic rats treated with 200 mg glutathione/kg body weight i. v. two times per week from weeks 0 to 10; and Group 4, of diabetic rats treated with placebo from weeks 0 to 4 and as Group 3 from weeks 4 to 10. The sensory and motor nerve conduction velocity of rats treated prophylactically with glutathione (Group 3) were significantly different from those of rats treated with placebo (Group 2) or with glutathione administered at a later time point (Group 4). Complete restoration of sensory and motor nerve conduction velocity was not reached. There was a significant improvement in motor nerve conduction velocity from weeks 4 to 6 (p〈0.005), but not in sensory nerve conduction velocity in the delayed treatment group (Group 4). In conclusion, treatment with glutathione, a free radical scavenger, is partially effective in the prevention of diabetic neuropathy in streptozotocin-induced diabetic rats, but is of limited value when the neuropathy is already present.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399926
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  • 7
    Electronic Resource
    Electronic Resource
    Randomized double-blind placebo-controlled trial to evaluate the effect of the ACTH4–9 analogue ORG 2766 in IDDM patients with neuropathy (1994)
    Springer
    Diabetologia 37 (1994), S. 408-413 
    Details
    ISSN: 1432-0428
    Keywords: Key words ACTH4–9 analogue, diabetic neuropathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study we report a randomized double-blind, placebo-controlled trial to evaluate the effect of ORG 2766 in IDDM patients with peripheral neuropathy. Sixty-two patients were selected based on the following criteria: abnormal vibration perception threshold above the 95th-percentile adjusted for age and/or abnormal warm temperature threshold, both measured in the right hand. The patients were randomized into two treatment groups after baseline studies: Group 1 was treated with placebo and Group 2 was treated with 3 mg of the ACTH4–9 analogue ORG 2766 every 24 h. The total study period was 1 year. After 1 year of treatment there was a significant improvement in vibration threshold in Group 1 compared to Group 2. No other parameters improved in the study period. The number of patients selected may have been too small to detect a more important treatment effect. We conclude from this study that ORG 2766 can improve vibration threshold, indicating large myelinated fibre function, but does not affect any the other neurophysiological function tests. [Diabetologia (1994) 37: 408–413]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408479
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    Reduced second phase insulin secretion in carriers of a sulphonylurea receptor gene variant associating with Type II diabetes mellitus (2000)
    Springer
    Diabetologia 43 (2000), S. 515-519 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type II diabetes mellitus, sulphonylurea receptor, genetics, insulin, beta cell, insulin secretion, impaired glucose tolerance, hyperglycaemic clamp.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The sulphonylurea receptor is a subunit of the ATP-sensitive potassium channel in the pancreatic beta cell. Mutations at nt –3 of the splice acceptor site of exon 16 and a silent mutation in exon 18 of the gene for the sulphonylurea receptor (SUR1) associate with Type II (non-insulin-dependent) diabetes mellitus in several independent populations. We investigated whether these gene variants associate with changes in the pattern of glucose-stimulated insulin secretion.¶Methods. Subjects who had normal glucose tolerance (n = 67) and subjects with an impaired glucose tolerance (n = 94), originating from two independent studies, were included in the study. Beta-cell function and insulin sensitivity were assessed by the hyperglycaemic clamp.¶Results. Frequencies of the exon 16 –3t allele in the normal and impaired glucose tolerant groups were 46 % and 44 % respectively (p = NS). The more rare exon 18 T allele showed frequencies of 5 and 7 % respectively (p = NS). We observed an approximately 25 % reduced second-phase insulin secretion in carriers of the exon 16 –3t allele in both groups (p 〈 0.05). Estimates of insulin sensitivity did not show differences between carriers and non-carriers. The variant in exon 18 and the combined presence of variants in exon 16 and exon 18 were not associated with differences in insulin secretion or insulin sensitivity in our study groups.¶Conclusion/interpretation. The diabetes associated exon 16 –3t variant of the SUR1 gene associates with a functional change of the beta cell as reflected by reduced second-phase insulin secretion in response to a standardized hyperglycaemia in normal and impaired glucose tolerant subjects. [Diabetologia (2000) 43: 515–519]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051337
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  • 9
    Electronic Resource
    Electronic Resource
    The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 405-410 
    Details
    ISSN: 1432-1041
    Keywords: Hyperlipidaemia ; Orlistat ; lipase inhibitor ; fat malabsorption ; LDL cholesterol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of orlistat, a nonabsorbed inhibitor of gastric and pancreatic lipases, was examined in patients with primary hyperlipidaemia (serum cholesterol ≥6.2 mmol·l−1 and triglycerides ≤5.0 mmol·l−1) not responsive to dietary change alone. In a multicentre, randomised, double-blind study, 103 men and 70 women received 30, 90, 180, or 360 mg of orlistat or placebo for 8 weeks. Total and low-density lipoprotein cholesterol levels were reduced by 4% and 5% with 30 mg orlistat, by 7% and 8% with 90 mg orlistat, by 7% and 7% with 180 mg orlistat and by 11% and 10% with 360 mg orlistat compared to placebo. High density lipoprotein cholesterol levels significantly decreased in the 360 mg orlistat group. Triglyceride levels significantly increased in the placebo group but not in the drug groups. Body weight decreased by 1.2 kg with 360 mg orlistat, despite a weight maintenance diet. Decreases in vitamin E and D levels occurred, although both vitamins remained within the normal range. Adverse effects from the gastrointestinal tract were frequent, but led to discontinuation of therapy in only seven patients. Orlistat is a new therapeutic drug for the treatment of hyperlipidaemia that may be particularly useful among overweight patients. Its potential place in therapy will await long-term studies. Vitamin supplementation should be considered during treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191901
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  • 10
    Electronic Resource
    Electronic Resource
    ACTH4–9 analogue ORG 2766 can improve existing neuropathy in streptozocin-induced diabetic rats (1993)
    Springer
    Acta diabetologica 30 (1993), S. 21-24 
    Details
    ISSN: 1432-5233
    Keywords: ACTH4–9 ; Experimental diabetic neuropathy ; Neuropeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of treatment of an existing neuropathy in streptozocin-induced diabetic rats with the ACTH4–9 analogue ORG 2766 was examined. Four groups of rats were studied: group 1 consisted of age-matched, non-diabetic controls and groups 2, 3 and 4 of diabetic rats. Sensory and motor nerve conduction velocity (SNCV and MNCV) were measured at weeks 0, 4, 6, 8 and 10. Four weeks after the administration of streptozocin (STZ) all diabetic rats showed a significant slowing of SNCV and MNCV. Treatment was then started: group 2 was treated with placebo, group 3 with a low dos (1 μg) of ACTH4–9 subcutaneously every 48h, and group 4 with a high dos (10 μg) of ACTH4–9 subcutaneously every 48 h. The animals treated with the high peptide dosage showed a significant improvement in both SNCV and MNCV from week 6 onwards, whereas this beneficial effect was not demonstrated for the rats treated with the low dosage. This study demonstrates that the ACTH4–9 analogue ORG 2766 can ameliorate existing diabetic neuropathy in STZ-induced diabetic rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00572869
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