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  • 1
    Electronic Resource
    Electronic Resource
    Model systems demonstrating the volatile mutagenicity and carcinogenicity of sodium nitrite in rats (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 554-557 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Volatile mutagens derived from sodium nitrite buffered at various pH values or in the presence of human feces were detected using AmesSalmonella tester strain TA 1535 on petrie plates inverted over samples. Volatile mutagenicity increased as the pH decreased and was primarily a function of the nitrous acid produced from sodium nitrite and hydrogen ions. Sodium nitrite administered intracecally to 3 Wistar rats through surgically implanted cannula caused tumors (fibrosarcoma: 1/3 and squamous cell, 2/3). The possible role of nitrite-derived mutagens in GI cancer is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01982327
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  • 2
    Electronic Resource
    Electronic Resource
    Thermoregulatory responses to hyperinsulinaemic hypoglycaemia and euglycaemia in IDDM (1994)
    Springer
    Diabetologia 37 (1994), S. 689-696 
    Details
    ISSN: 1432-0428
    Keywords: Key words Blood glucose, body temperature, diabetes mellitus insulin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In healthy subjects hypoglycaemia causes a fall in body temperature through increased sweating and limb blood flow, and despite increased metabolic heat production. We studied thermoregulatory responses to hyperinsulinaemic (100 mU·m−2·min−1) (a) hypoglycaemia (2.5 mmol/l) and (b) euglycaemia (4.5 mmol/l) in insulin-dependent diabetic men of short ( 〈5 years) and long (〉15 years) diabetes duration. Plasma noradrenaline (p〈0.0001), metabolic rate (p〈0.005), heart rate (p〈0.0001) and skin blood flow (p〈0.05) increased during hypoglycaemia and euglycaemia with a greater rise in noradrenaline during the former (p〈0.05). Plasma adrenaline (p〈0.005), forearm blood flow (p〈0.05) and systolic blood pressure (p〈0.02) increased and diastolic blood pressure decreased (p〈0.005) during hypoglycaemia, with greater changes in adrenaline (p〈0.05) and diastolic blood pressure in patients of short diabetes duration. Only two patients (diabetes duration 〈2 years) sweated appropriately, while body temperature changed minimally in the two groups of patients. In summary, thermoregulatory responses to hypoglycaemia are impaired in IDDM due to attenuated sweating and adrenomedullary responses. [Diabetologia (1994) 37: 689–696]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00417693
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  • 3
    Electronic Resource
    Electronic Resource
    Adaptation to mild hypoglycaemia in normal subjects despite sustained increases in counter-regulatory hormones (1989)
    Springer
    Diabetologia 32 (1989), S. 249-254 
    Details
    ISSN: 1432-0428
    Keywords: Counter-regulation ; hypoglycaemia ; catecholamines ; glucagon ; hypoglycaemic unawareness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In diabetes, loss of awareness of and a defective hormonal response to hypoglycaemia have been associated with long disease duration, improved glycaemic control and possibly a change in insulin species. In contrast it is assumed that normal subjects always have symptoms when their blood glucose is low. We have tested this in 7 normal subjects at 3 levels of blood glucose (4.5, 3.5 and 3.0 mmol/l) using a hyperinsulinaemic glucose clamp with a euglycaemic (4.5 mmol/l) clamp as a control. After 60 min at a blood glucose of 3.5 mmol/l adrenaline and glucagon increased slightly but significantly, whereas cortisol, growth hormone and pancreatic polypeptide were unchanged. As soon as glucose was lowered to 3.0 mmol/l adrenaline increased to 1.10 nmol/l and rose further to 1.43 nmol/l after 60 min. Glucagon secretion increased similarly but other counter-regulatory hormones were significantly raised only after 60 min at 3.0 mmol/l. Awareness of hypoglycaemia (symptom score) increased after 40 min at a blood glucose of 3.0 mmol/l but after 60 min decreased to baseline levels with loss of awareness in 5 subjects. Reaction time improved in parallel with the change in symptom score. Thus, despite high levels of adrenaline, normal subjects lose awareness during sustained mild hypoglycaemia. Improved reaction time may reflect cerebral adaptation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00285293
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  • 4
    Electronic Resource
    Electronic Resource
    Physiological response to postural change during mild hypoglycaemia in patients with IDDM (1994)
    Springer
    Diabetologia 37 (1994), S. 1241-1250 
    Details
    ISSN: 1432-0428
    Keywords: Posture ; insulin-dependent diabetes mellitus ; hypoglycaemia ; adrenaline ; adaptation to hypoglycaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been suggested that patients with insulin-dependent diabetes mellitus may be less aware of impending hypoglycaemia when lying than standing. We have studied the effect of posture and duration of hypoglycaemia on symptoms and physiological responses in 10 men with insulin-dependent diabetes. A standard tilting protocol was used (supine, 50
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399798
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  • 5
    Electronic Resource
    Electronic Resource
    Physiological response to postural change during mild hypoglycaemia in patients with IDDM (1994)
    Springer
    Diabetologia 37 (1994), S. 1241-1250 
    Details
    ISSN: 1432-0428
    Keywords: Key words Posture ; insulin-dependent diabetes mellitus ; hypoglycaemia ; adrenaline ; adaptation to hypoglycaemia.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been suggested that patients with insulin-dependent diabetes mellitus may be less aware of impending hypoglycaemia when lying than standing. We have studied the effect of posture and duration of hypoglycaemia on symptoms and physiological responses in 10 men with insulin-dependent diabetes. A standard tilting protocol was used (supine, 50 °, 90 ° headup, and return to supine, 5 min at each position). At one visit patients were tilted before, 10 min after and 40 min after achieving hypoglycaemia (blood glucose 2.5 mmol/l), and at another visit were tilted after euglycaemia (5.0 mmol/l) using a hyperinsulinaemic clamp. At each position, hormonal and physiological responses and symptoms (using visual analogue scales) were recorded. After 10 min of hypoglycaemia, adrenaline was significantly higher when 90 ° headup compared with supine (mean [ ± SEM] 6.26 [ ± 1.88] vs 1.68 [ ± 0.4] nmol/l; p 〈 0.05), and fell significantly (to 2.46 [ ± 0.65] nmol/l; p 〈 0.05) when returned to supine; sweating, symptom score and blood pressure followed a similar pattern. After 40 min of hypoglycaemia a similar effect of standing was seen on sweating, adrenaline and blood pressure but symptoms did not increase. Five patients underwent two further periods of hypoglycaemia, remaining supine or standing throughout. Face skin blood flow (p 〈 0.05) and temperature (p = 0.05) decreased when standing was maintained compared with lying. In conclusion, standing increases awareness of early hypoglycaemia and modifies many of the physiological changes. This increase in awareness is lost if hypoglycaemia is prolonged. [Diabetologia (1994) 37: 1241–1250]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399798
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  • 6
    Electronic Resource
    Electronic Resource
    Gender differences in counterregulation to hypoglycaemia (1993)
    Springer
    Diabetologia 36 (1993), S. 460-464 
    Details
    ISSN: 1432-0428
    Keywords: Counterregulation ; hypoglycaemia ; gender ; catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the effect of gender on catecholamine responses to hypoglycaemia, single-step euglycaemic-hypoglycaemic clamps have been performed in 14 healthy men and 17 women. Adrenaline responses were 44% lower in females (p〈0.01) and noradrenaline 17% lower (p=0.08). In response to low-dose intravenous insulin infusion (0.3 mU · kg−1 · min−1), plasma glucose fall and counter-regulation in seven men and seven women had a different course (p〈0.001), with different glucose kinetics. In men, endogenous glucose output recovered quickly to levels that exceeded basal; in women suppression of endogenous glucose output was more prolonged, without rates ever exceeding basal (p〈0.05). Peripheral glucose uptake was stimulated in men only. The hormones of acute glucose counter-regulation (catecholamines and glucagon) did not differ between the sexes during this challenge, the catecholamine response in the women being supported by the continuous fall in plasma glucose. These results suggest that: 1) catecholamine responses to moderately controlled hypoglycaemia are diminished in women, and 2) Peripheral insulin sensitivity in men is enhanced over that of women but hepatic sensitivity to insulin may be greater in women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402284
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  • 7
    Electronic Resource
    Electronic Resource
    Prolonged but partial impairment of the hypoglycaemic physiological response following short-term hypoglycaemia in normal subjects (1995)
    Springer
    Diabetologia 38 (1995), S. 1183-1190 
    Details
    ISSN: 1432-0428
    Keywords: Key words Antecedent hypoglycaemia ; catecholamines ; counterregulation ; hypoglycaemia ; hypoglycaemia unawareness.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent studies have reported reduced endocrine and symptomatic responses to hypoglycaemia 18–24 h after antecedent hypoglycaemia in both non-diabetic subjects and those with insulin-dependent diabetes mellitus. We examined these and peripheral physiological responses in eight non-diabetic subjects aged 23–35 years in the week following antecedent hypoglycaemia. Blood glucose levels were held at plateaus of 5 mmol/l and 2.5 mmol/l for 30 min during hyperinsulinaemic (60 mU · m−2· min−1) morning clamps on days 1, 3 and 8 of two study periods separated by at least 4 weeks. Measurements were made at time 0, 15 and 30 min of each plateau on each day. On the afternoon of Day 1 we also induced either euglycaemia with a blood glucose level of 5 mmol/l (control week) or hypoglycaemia of 2.9 mmol/l (hypo week) for 2 h in random order. The adrenaline response to morning hypoglycaemia (p 〈 0.01 on all days) was attenuated on Day 3 (p 〈 0.05) and Day 8 (p 〈 0.05) compared to Day 1 of hypo week only. Sweating was also attenuated on Day 3 (p 〈 0.05) and Day 8 (p 〈 0.02) of hypo week only. Noradrenaline levels and tremor increased during hypoglycaemia on each study day (p 〈 0.05) but did not differ between days in either week. During hypo week only, the total symptom score response to hypoglycaemia was attenuated on Day 3 (p 〈 0.03) but not Day 8 (p = 0.10). Autonomic symptoms were similarly affected. In summary, the physiological responses to hypoglycaemia are affected differentially by antecedent hypoglycaemia with sweating and adrenaline responses remaining impaired for at least 5 days. [Diabetologia (1995) 38: 1183–1190]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422367
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  • 8
    Electronic Resource
    Electronic Resource
    Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM (1997)
    Springer
    Diabetologia 40 (1997), S. 82-88 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; gastric emptying ; postprandial hyperglycaemia ; amylin ; pramlintide.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pramlintide, a human amylin analogue, reduces hyperglycaemia after meals in patients with insulin-dependent diabetes mellitus (IDDM). We investigated whether this was due to delayed gastric emptying. Eight men with uncomplicated IDDM were studied twice in a randomised, double-blind crossover design. Euglycaemia was maintained overnight by intravenous infusion of glucose and/or insulin and the following morning a 5-h infusion of pramlintide 25 μg/h or placebo was started at 08.00 hours. At 08.30 hours the patients injected their normal morning insulin dose subcutaneously and 30 min later ate a meal (600 kcal, 50 % carbohydrate) of which the solid component was labelled with Technetium-99 m and the liquid with Indium-111 to quantify gastric emptying. Gamma-scintigraphic images were obtained every 20 min for the next 4 h. Insulin and glucose were infused as necessary to maintain blood glucose levels within 3 mmol/l of the pre-meal value. Compared to placebo, pramlintide significantly delayed emptying of both liquid (median lag time 69 vs 7.5 min) and solid (median lag time 150 vs 44.5 min) components of the meal. Pramlintide delayed gastric emptying so much that t50 values could not be calculated for solid or liquid. Amylin agonists such as pramlintide may, therefore, be of value in improving glycaemic control in IDDM by modifying gastric emptying. [Diabetologia (1997) 40: 82–88]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050646
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  • 9
    Electronic Resource
    Electronic Resource
    Euglycaemic hyperinsulinaemia does not affect gastric emptying in Type I and Type II diabetes mellitus (1999)
    Springer
    Diabetologia 42 (1999), S. 365-372 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; Type II diabetes ; euglycaemia ; hyperinsulinaemia ; gastric emptying.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyperglycaemia slows gastric emptying in both normal subjects and patients with diabetes mellitus. The mechanisms mediating this effect, particularly the potential role of insulin, are uncertain. Hyperinsulinaemia has been reported to slow gastric emptying in normal subjects during euglycaemia. The purpose of this study was to evaluate the effect of euglycaemic hyperinsulinaemia on gastric emptying in Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus. In six patients with uncomplicated Type I and eight patients with uncomplicated Type II diabetes mellitus, measurements of gastric emptying were done on 2 separate days. No patients had gastrointestinal symptoms or cardiovascular autonomic neuropathy. The insulin infusion rate was 40 mU · m–2· min–1 on one day and 80 mU · m–2· min–1 on the other. Gastric emptying and intragastric meal distribution were measured using a scintigraphic technique for 3 h after ingestion of a mixed solid/liquid meal and results compared with a range established in normal volunteers. In both Type I and Type II patients the serum insulin concentration had no effect on gastric emptying or intragastric meal distribution of solids or liquids. When gastric emptying during insulin infusion rates of 40 mU · m–2· min–1 and 80 mU · m–2· min–1 were compared the solid T50 was 137.8 ± 24.6 min vs 128.7 ± 24.3 min and liquid T50 was 36.7 ± 19.4 min vs 40.4 ± 15.7 min in the Type I patients; the solid T50 was 94.9 ± 19.1 vs 86.1 ± 10.7 min and liquid T50 was 21.8 ± 6.9 min vs 21.8 ± 5.9 min in the Type II patients. We conclude that hyperinsulinaemia during euglycaemia has no notable effect on gastric emptying in patients with uncomplicated Type I and Type II diabetes; any effect of insulin on gastric emptying in patients with diabetes is likely to be minimal. [Diabetologia (1999) 42: 365–372]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051164
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  • 10
    Electronic Resource
    Electronic Resource
    Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia (1992)
    Springer
    Diabetologia 35 (1992), S. 287-290 
    Details
    ISSN: 1432-0428
    Keywords: Hypoglycaemia ; euglycaemia ; insulin ; arterial ; arterialized venous ; venous and capillary blood glucose ; blood oxygen saturation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to evaluate the effectiveness of the warm-air box method on the arterialization of venous blood during euglycaemia and hypoglycaemia. Six healthy male volunteers were studied using an i.v. infusion of insulin (144 mU·kg−1·h−1). Arterial blood glucose was clamped at the baseline level for the first 30 min and subsequently reduced to 3.2 and to 2.5 mmol/l for 20 min. At each stage, including prior to insulin infusion, arterial, arterialized venous (heating the hand in a warm-air box set to 55–60°C), venous and capillary blood samples were taken simultaneously for analyses of blood glucose and oxygen saturation (not for capillary blood). The oxygen saturations in arterialized blood were approximately 3% below the arterial values. The arterial-arterialized difference of blood glucose was about 0.1 mmol/l (the 95% confidence interval: from −0.19 to 0.41 mmol/l), which tended to correlate with the difference in oxygen saturations between the arterial and arterialized blood samples (r=0.25, p=0.08). During the test the forearm venous blood oxygen saturation increased by 9% and the arteriovenous difference in blood glucose ranged from 0.2 to 0.5 mmol/l which correlated significantly with the difference in oxygen saturations (r=0.48, p〈0.001). Capillary glucose was similar to the arterialized value. Rectal temperature was stable during the experiment. We conclude that the heated hand technique using the warm-air box sufficiently arterializes venous blood so that the glucose measurement in the arterialized blood provides a reasonable estimate of the arterial value and that the venous blood from the contralateral forearm is also markedly arterialized, probably reflecting a vasodilator effect of heating.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400932
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