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  • 1
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes ; autonomic neuropathy ; graded exercise ; heart rate ; blood pressure ; cardiac output ; cardiac stroke volume ; plasma volume ; hepato-splanchnic blood flow ; body temperature ; plasma catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Haemodynamic variables were measured during supine rest and during ergometer cycle exercise at two work loads (50 W and 100 W) in normal subjects (n = 7), in insulin-dependent diabetic subjects without neuropathy (n = 8), in insulin-dependent diabetic subjects with slight autonomic neuropathy (decreased beat-to-beat variation in heart rate, which is considered due to a cardiac parasympathetic defect; n = 8), and in insulin-dependent diabetic subjects with severe autonomic neuropathy, including orthostatic hypotension (n = 7). Compared with normal subjects, cardiac stroke volume was lower in the diabetic subjects with autonomic neuropathy, both at rest and during exercise (p 〈 0.025), whereas intermediate values were found in the diabetic subjects without neuropathy. The increase in cardiac output in response to exercise was smaller (p 〈 0.05) in both diabetic groups with autonomic neuropathy compared with the normal and diabetic subjects without autonomic neuropathy. The increase in hepato-splanchnic vascular resistance was smaller in the diabetic subjects with severe autonomic neuropathy than in the normal subjects and the diabetic subjects without autonomic neuropathy (p 〈 0.025), whereas intermediate values were found in the diabetic subjects with slight autonomic neuropathy. We conclude that, in diabetic patients with severe autonomic neuropathy, the responses of the heart and the splanchnic resistance vessels to exercise are impaired. While sympathetic neuropathy may be responsible for impaired function of splanchnic resistance vessels, both cardiac sympathetic neuropathy and diabetic cardiomyopathy may be involved in the impaired cardiac response to exercise in diabetic subjects with autonomic neuropathy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: IDDM ; diabetic autonomic neuropathy ; prevalence ; simple bedside tests ; nerve function ; retinopathy ; nephropathy ; diabetic complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the prevalence of diabetic autonomic neuropathy, five simple bedside tests, beat-to-beat variation during quiet respiration, beatto-beat variation during forced respiration, heart rate and blood pressure response to standing, heart rate response to exercise, and heart rate response to Valsalva's manoeuvre were applied to 75 male insulindependent diabetics, mean age 40 years, (range 30–49 years). The subjects were subdivided into three groups according to duration of diabetes, which was between 0 and 40 years. Twenty-eight healthy age-matched male controls were also studied. The prevalence of diabetic autonomic neuropathy in the whole diabetic population indicated by abnormal response in beat-to-beat variation during forced respiration was 27%. Diabetic autonomic neuropathy increased in frequency with duration of disease. Patients with nephropathy or proliferative retinopathy had a significantly higher prevalence of diabetic autonomic neuropathy as indicated by abnormal beat-to-beat variation during forced respirations (p〈0.01) than patients without these complications.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; hypoglycaemia ; B cell function ; glucagon ; glucose recovery ; lipolysis ; ketogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hormonal, metabolic and cardiovascular responses to insulin induced hypoglycaemia were investigated in seven Type 1 (insulin-dependent) diabetic patients with residual B cell function, eight Type 1 diabetic patients without B cell function and six healthy subjects. No differences were found between the diabetic groups regarding nadir of glucose and rate of recovery to normoglycaemia. The patients with residual B cell function had a glucagon response to hypoglycaemia which was close to that of normal subjects. In patients without B cell function, the glucagon response to hypoglycaemia was present, albeit significantly smaller than in the patients with preserved B cell function (0.025 ng/ml, range 0.007–0.042 versus 0.054 ng/ml, range 0.029–0.087). The group without B cell function had signs of an exaggerated rate of lipolysis and ketogenesis compared with the patients with B cell function and the normal subjects.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 32 (1989), S. 888-888 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Intranasal insulin administration ; absorption enhancers ; metabolic control ; subcutaneous insulin administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Key words Intranasal insulin administration ; absorption enhancers ; metabolic control ; subcutaneous insulin administration.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, cross-over randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time. [Diabetologia (1995) 38: 680–684]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Adrenaline ; autonomic neuropathy ; catecholamine ; kinetics ; Type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma adrenaline kinetics (clearance, extraction across the forearm, initial plasma disappearance rate, mean sojourn time, volume of distribution) were studied in sixteen Type 1 (insulin-dependent) diabetic patients during constant i.v. infusion of tritium labelled adrenaline. In patients with (n=8) and without (n=8) neuropathy forearm venous plasma noradrenaline and adrenaline concentrations as well as plasma clearance of adrenaline based on arterial sampling (1.7 vs 2.1 l/min) were not significantly different. The initial disappearance time (T1/2) after the infusion of the tritium labelled adrenaline had been stopped was significantly prolonged in Type 1 diabetic patients with neuropathy compared to those without (after 20 min infusion 2.7 vs 2.2 min, p〈0.02, after 75 min infusion 3.7 vs 2.9 min, p〈0.05). The corresponding values for the mean sojourn time of adrenaline in plasma were 6.5 vs 4.7 min (p〈0.05) after 20 min infusion and 18 vs 10 min (p〈0.05) after 75 min of infusion. The unchanged plasma clearance and the prolonged initial halftime and mean sojourn time of adrenaline in plasma suggest that adrenaline is distributed in a larger volume in Type 1 diabetic patients with neuropathy as compared to patients without neuropathy (estimated space of distribution 29 vs 201). Our results suggest that patients with diabetic neuropathy do not adjust the plasma adrenaline concentration to changes in adrenaline infusion rate as rapidly as those without neuropathy, i. e. the effect of an elevated adrenaline secretion rate may be prolonged in patients with diabetic autonomic neuropathy.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 35 (1992), S. 99-103 
    ISSN: 1432-0428
    Keywords: Adrenaline ; capillary permeability ; diabetes mellitus ; haematocrit ; insulin ; noradrenaline ; plasma volume ; transcapillary albumin transport ; urinary albumin excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the past decade it has been demonstrated that insulin, apart from its effects on metabolism and ion fluxes, has acute effects on the cardiovascular system and capillary permeability. Intravenous infusion of insulin in doses which increase plasma insulin to physiological levels, induced vascular dilatation and increased muscle sympathetic nerve activity during a euglycaemic glucose clamp. During similar conditions insulin increased the transcapillary escape rate of albumin and reduced plasma volume. Insulin has also an indirect effect on vascular permeability during hypoglycaemia, which is mediated by the increase in plasma adrenaline. Adrenaline infusion increased haematocrit and decreased plasma volume and intravascular albumin mass. In contrast to insulin adrenaline did not increase the transcapillary escape rate of albumin. Total autonomic blockade during insulin-induced hypoglycaemia abolished the increase in haematocrit, but did not influence the decrease in plasma volume and the increase in the transcapillary escape rate of albumin. Insulin administration may also increase urinary albumin excretion, and this effect was observed during a euglycaemic clamp. The mechanism of the increase in capillary permeability after insulin has not been elucidated. A number of morphological studies indicate that insulin may have effects on endothelial cell morphology and paraendothelial cell permeability. These results indicate that insulin, apart from its effect on peripheral blood flow, may play a role in a normal transfer of macromolecules from the blood to the extracellular space after food intake. This process may be greatly disturbed in insulin-dependent diabetic patients.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 46 (1994), S. 15-17 
    ISSN: 1432-1041
    Keywords: Hypoglycaemia ; Glucagon ; intranasal ; glucose appearance rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We compared the hyperglycaemic effect of intranasal and intramuscular (i.m.) administration of glucagon after insulin-induced hypoglycaemia. Twelve healthy subjects were examined twice, receiving on both occasions an intravenous insulin bolus. Somatostatin and propranolol were administered to block endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose to exceed 3 mmol·l−1 was significantly shorter for i.m. glucagon. The mean plasma glucagon level increased faster after i.m. glucagon than after intranasal glucagon, and the levels remained higher throughout the study period. We conclude that glucose recovery was significantly better after i.m. administration of glucagon than after intranasal administration. However, the differences between the incremental plasma glucose and the time for incremental plasma glucose to exceed 3 mmol·l−1 were not considered of major clinical importance.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We assessed HLA-DR types and investigated serum samples for islet-cell cytoplasmic antibodies (ICA) in 31 Danish patients with chronic pancreatitis. The antigen frequencies were compared with those in 1177 unrelated healthy Danish controls. Twenty patients had insulin-dependent diabetes and 11 had normal intravenous glucose tolerance. No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin-dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. ICA were negative in all patients with chronic pancreatitis. It is concluded that the beta-cell dysfunction in insulin-dependent diabetes in chronic pancreatitis differs from that of classical insulin-dependent diabetes.
    Type of Medium: Electronic Resource
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