Insulin analogues and carcinoma of the breast.
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Animals↗
Biomedical subjects
P Ebeling
Publications and source records attributed to P Ebeling.
Postmarathon paradox: insulin resistance in the face of glycogen depletion.
Acute physical exercise enhances insulin sensitivity in healthy subjects. We examined the effect of a 42-km marathon run on insulin sensitivity and lipid oxidation in 19 male runners. In the morning after the marathon run, basal serum free fatty acid concentration was 2.2-fold higher, muscle glycogen content 37% lower (P < 0.01), glycogen synthase fractional activity 56% greater (P < 0.01), and glucose oxidation reduced by 43% (P < 0.01), whereas lipid oxidation was increased by 55% (P < 0.02) compared with the control study. During euglycemic-hyperinsulinemic clamp, whole body glucose disposal was decreased by 12% (P < 0.01) because of a 36% lower glucose oxidation rate (P < 0.05), whereas the rate of lipid oxidation was 10-fold greater (P < 0.02) than in the control study. After the marathon, muscle glycogen content correlated positively with lipid oxidation (r = 0.60, P < 0.05) and maximal aerobic power (Vo2peak; r = 0.61, P < 0.05). Vo2peak correlated positively with basal lipid oxidation (r = 0.57, P < 0.05). In conclusion, 1) after the marathon run, probably because of increased lipid oxidation, the insulin-stimulated glucose disposal is decreased despite muscle glycogen depletion and the activation of glycogen synthase; 2) the contribution of lipid oxidation in energy expenditure is increased in proportion to physical fitness; 3) these adaptations of fuel homeostasis may contribute to the maintenance of physical performance after prolonged exercise.
Adult↗
Immune brachial plexus neuropathy: suggestive evidence for an inflammatory-immune pathogenesis.
We report brachial plexus biopsy findings from two Australian and two American patients with brachial plexus neuropathy. There were florid multifocal mononuclear inflammatory cell infiltrates. Present evidence suggests that these brachial neuropathies have an immune basis.
Adult↗
Cardiovascular disease and its risk factors in IDDM in Europe. EURODIAB IDDM Complications Study Group.
OBJECTIVE: To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS: The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean +/- SD duration of diabetes was 14.7 +/- 9.3 years. RESULTS: The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15-29 years old to 25% in patients 45-59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA1c, prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS: The overall prevalence of CVD in these IDDM patients was approximately 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.
Adolescent↗
Androgens and insulin resistance in type 1 diabetic men.
OBJECTIVE: In healthy men, both high and low serum testosterone concentrations are associated with insulin resistance, whereas low concentration of sex hormone binding globulin (SHBG) is related to reduced insulin sensitivity. The aim of our study was to examine the association of sex hormones, SHBG, dehydroepiandrosterone (DHEAS) and insulin-like growth factor binding protein-1 (IGFBP-1) on insulin sensitivity in type 1 diabetic patients. PATIENTS: We examined 23 male patients with the mean age of 29 +/- 1 years, body mass index 22.9 +/- 0.4 kg/m2, insulin dose 47 +/- 3 units/day, glycosylated haemoglobin (HbA1c) 7.8 +/- 0.3% and duration of diabetes 13 +/- 1 years. DESIGN: Each patient was studied with a 4-hour euglycaemic (5.5 +/- 0.1 mmol/l), hyperinsulinaemic (612 +/- 26 pmol/l) clamp with indirect calorimetry. Muscle biopsies (quadriceps femoris) for the determination of glycogen synthase were performed in 15 patients before and at the end of the clamp. RESULTS: Insulin infusion reduced the concentrations of IGFBP-1 by 90% (P < 0.001), DHEAS by 11% (P < 0.001), and SHBG by 4% (P < 0.01), whereas free or bound testosterone levels remained unchanged. The fall in IGFBP-1 level was closely related to the basal concentration (r = 0.99, P < 0.001). Basal SHBG concentration correlated directly with total (r = 0.51, P < 0.05) and non-oxidative glucose disposal (r = 0.41, P < 0.05), and with the decrease in lipid oxidation (r = 0.47, P < 0.05) during insulin infusion. The fall in SHBG was inversely related to the mean (30-240 min) FFA concentration during hyperinsulinaemia (r = -0.64, P < 0.001). The fractional activity of glycogen synthase at the end of insulin infusion correlated directly with fasting SHBG (r = 0.71, P < 0.01) and DHEAS concentrations (r = 0.67, P < 0.01). CONCLUSIONS: In male type 1 diabetic patients: (1) acute hyperinsulinaemia decreases IGFBP-1, DHEAS and SHBG concentrations with the greatest decline in IGFBP-1, (2) SHBG concentration is positively associated with factors indicating good insulin sensitivity, (3) association between fuel homeostasis and SHBG, DHEAS and insulin antagonists suggests a network of these factors in the regulation of insulin action in type 1 diabetic patients.
Adult↗
Acute hyperinsulinemia, androgen homeostasis and insulin sensitivity in healthy man.
The acute effects of hyperinsulinemia on androgen homeostasis and a possible association of androgens to insulin sensitivity, serum lipids and lipoproteins and to lipid oxidation were examined in 19 healthy males (27 +/- 1 yrs, body mass index 24 +/- 1 kg/m2). In each subject, a 240 min euglycemic hyperinsulinemic clamp was performed and glucose and lipid oxidation were determined by indirect calorimetry. During hyperinsulinemia serum sex hormone-binding globulin (SHBG) concentration decreased by 5% (P < 0.01), insulin-like growth factor binding protein (IGFBP-1) by 88% (P < 0.001) and dehydroepiandrosterone sulphate (DHEAS) by 12% (P < 0.001), with no change in total or free testosterone concentrations. In the basal state, IGFBP-1 and C-peptide were inversely related (r = -0.54, P < 0.05). Fasting concentrations of serum free testosterone (r = 0.59, P < 0.01) and DHEAS (r = 0.47, P < 0.05) correlated positively with serum free fatty acid (FFA) concentrations during hyperinsulinemia, but not with fasting FFA level. Lipid oxidation rate in the basal state correlated positively to the decline in SHBG (r = 0.61, P < 0.01) and DHEAS concentrations (r = 0.62, P < 0.01) during hyperinsulinemia. While the fasting serum high density lipoprotein cholesterol level correlated positively with the insulin-induced decline in DHEAS level (r = 0.58, P < 0.01), no associations were found between serum androgens and total cholesterol, low density lipoprotein cholesterol or triglyceride concentrations. Insulin sensitivity was not related to SHBG, IGFBP-1, DHEAS or testosterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Athletes with IDDM exhibit impaired metabolic control and increased lipid utilization with no increase in insulin sensitivity.
Physical exercise is traditionally recommended to diabetic patients as part of their treatment. Although healthy athletes exhibit enhanced skeletal muscle insulin sensitivity, the metabolic effects of vigorous training in patients with insulin-dependent diabetes mellitus (IDDM) are not known. This study was designed to examine the effects of competitive sports on fuel homeostasis and insulin sensitivity in athletes with IDDM. We studied 11 athletes and 12 matched sedentary men with IDDM. In each subject, we measured glycemic control, insulin-stimulated glucose uptake in the whole body and forearm, rates of glucose and lipid oxidation, and muscle glycogen, glycogen synthase, and glucose transport protein (GLUT4) concentrations. The athletes had higher VO2max (52 +/- 1 vs. 42 +/- 1 ml.kg-1.min-1, P < 0.001) and HbA1c levels (8.4 +/- 0.4 vs. 7.2 +/- 0.2%, P < 0.05) than sedentary patients, but took smaller insulin doses (41 +/- 3 vs. 53 +/- 3 U/day, P < 0.05). The insulin-stimulated rates of whole-body and forearm glucose uptake and glucose oxidation were similar in the two groups, whereas both energy expenditure and lipid oxidation were increased in the athletes. Lipid oxidation correlated inversely with glycogen synthase activity. The mean glucose arterialized venous blood-deep venous blood (A-V) difference during the insulin infusion (60-240 min) correlated with the whole-body glucose disposal throughout the insulin infusion (after 60 min, r > 0.73, P < 0.001 for all 30-min periods). This association is accounted for by the relationship between glucose A-V difference and nonoxidative glucose disposal. Muscle glycogen and GLUT4 protein contents were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Physiological importance of dehydroepiandrosterone.
Dehydroepiandrosterone (DHEA), with its sulphate conjugate (DHEAS), is the most abundant steroid hormone in the circulation but its physiological importance is unclear. We propose that DHEA has either oestrogen-like or androgen-like effects depending on the hormonal milieu. In premenopausal women DHEA is either an oestrogen antagonist, perhaps through the competitive binding of its metabolite 5-androstene-3 beta, 17 beta-diol (ADIOL) and oestradiol to the oestrogen receptor, or an androgen through its metabolism to androstenedione and testosterone. In women DHEA contributes to abdominal obesity and insulin resistance: in the premenopausal high oestrogen concentrations may counterbalance the androgenic effects of DHEA but in the postmenopausal metabolism to testosterone may increase the risk of cardiovascular disease, though this effect may be counterbalanced by the age-dependent decline in DHEA and also by the oestradiol-like effects of ADIOL. In some breast cancer cell lines in a low oestrogen milieu DHEA has an oestradiol-like effect, stimulating tumour growth, whereas in oestradiol abundance DHEA antagonises the growth-stimulating effect of oestradiol. In men, with an androgenic milieu, DHEA acts like an oestrogen and protects against cardiovascular disease.
Breast Neoplasms↗
Non-esterified fatty acids regulate lipid and glucose oxidation and glycogen synthesis in healthy man.
UNLABELLED: We examined the interrelationship of lipid and glucose metabolism in the basal state and during insulin stimulus in 19 healthy men (27 +/- 2 years, body mass index 23.6 +/- 0.6 kg/m2). In each subject, we performed a 4-h euglycaemic (5.3 +/- 0.1 mmol/l) hyperinsulinaemic (647 +/- 21 pmol/l) insulin clamp with indirect calorimetry in the basal state and during insulin infusion, and muscle biopsies before and at the end of the clamp. In the basal state, serum non-esterified fatty acid levels correlated directly with lipid oxidation (r = 0.56, p < 0.05) and indirectly with glucose oxidation (r = -0.80, p < 0.001). Lipid and glucose oxidation rates were inversely related in the basal state (r = -0.47, p < 0.05) and during insulin infusion (r = -0.65, p < 0.01). Basal lipid oxidation and glycogen synthase total activity correlated inversely (r = -0.54, p < 0.05). Lipid oxidation both in the basal state (r = -0.61, p < 0.01) and during insulin infusion (r = -0.62, p < 0.05) was inversely related to muscle glycogen content after the insulin clamp. Fasting plasma triglyceride concentration correlated directly to fasting insulin (r = 0.55, p < 0.05) and C-peptide (r = 0.50, p < 0.03) concentrations and inversely to non-oxidative glucose disposal rate at the end of clamp (r = -0.54, p < 0.05). IN CONCLUSION: 1) Serum non-esterified fatty acid concentration enhances lipid and reduces glucose oxidation. 2) Lipid oxidation is inversely related to total glycogen synthase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Mechanism of enhanced insulin sensitivity in athletes. Increased blood flow, muscle glucose transport protein (GLUT-4) concentration, and glycogen synthase activity.
UNLABELLED: We examined the mechanisms of enhanced insulin sensitivity in 9 male healthy athletes (age, 25 +/- 1 yr; maximal aerobic power [VO2max], 57.6 +/- 1.0 ml/kg per min) as compared with 10 sedentary control subjects (age, 28 +/- 2 yr; VO2max, 44.1 +/- 2.3 ml/kg per min). In the athletes, whole body glucose disposal (240-min insulin clamp) was 32% (P < 0.01) and nonoxidative glucose disposal (indirect calorimetry) was 62% higher (P < 0.01) than in the controls. Muscle glycogen content increased by 39% in the athletes (P < 0.05) but did not change in the controls during insulin clamp. VO2max correlated with whole body (r = 0.60, P < 0.01) and nonoxidative glucose disposal (r = 0.64, P < 0.001). In the athletes forearm blood flow was 64% greater (P < 0.05) than in the controls, whereas their muscle capillary density was normal. Basal blood flow was related to VO2max (r = 0.63, P < 0.05) and glucose disposal during insulin infusion (r = 0.65, P < 0.05). The forearm glucose uptake in the athletes was increased by 3.3-fold (P < 0.01) in the basal state and by 73% (P < 0.05) during insulin infusion. Muscle glucose transport protein (GLUT-4) concentration was 93% greater in the athletes than controls (P < 0.01) and it was related to VO2max (r = 0.61, P < 0.01) and to whole body glucose disposal (r = 0.60, P < 0.01). Muscle glycogen synthase activity was 33% greater in the athletes than in the controls (P < 0.05), and the basal glycogen synthase fractional activity was closely related to blood flow (r = 0.88, P < 0.001). IN CONCLUSION: (a) athletes are characterized by enhanced muscle blood flow and glucose uptake. (b) The cellular mechanisms of glucose uptake are increased GLUT-4 protein content, glycogen synthase activity, and glucose storage as glycogen. (c) A close correlation between glycogen synthase fractional activity and blood flow suggests that they are causally related in promoting glucose disposal.
Adult↗
Seven years of remission in a type I diabetic patient.
OBJECTIVE: To analyze factors contributing to a long-term remission in a patient with type I diabetes. RESEARCH DESIGN AND METHODS: The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow-up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and beta-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects. RESULTS: Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr. CONCLUSIONS: In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr.
Adolescent↗
Eosinophilic meningitis due to Angiostrongylus cantonensis.
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Adult↗
Cardiogenic brain embolism: role of anticoagulants.
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Anticoagulants↗
Anti-neutrophil cytoplasmic antibodies associated with atrial myxoma.
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Adult↗
Glucose and lipid metabolism and insulin sensitivity in type 1 diabetes: the effect of guar gum.
The effect of guar gum on glucose and lipid metabolism and on body insulin sensitivity was examined in nine type 1 diabetic patients treated with continuous subcutaneous insulin infusion. The study was done in a randomized, double-blind, crossover fashion with either guar gum or a placebo added to the usual diet four times per day for 4 wk each. Blood glucose levels after breakfast and lunch and daily insulin requirements were significantly lower during the guar-gum than the placebo diet. After a 4-wk guar-gum supplementation, blood glucose response to a test meal was significantly reduced by guar gum compared with the placebo. Hemoglobin A1 (HbA1) and insulin sensitivity remained unchanged. Serum total cholesterol fell by 21% (p less than 0.025). Thus, guar gum can reduce postprandial blood glucose, insulin requirements, and serum total cholesterol levels in type 1 diabetic patients.
Adult↗
Spontaneous internal carotid artery dissection presenting as hypoglossal nerve palsy.
A 42-year-old man presented with right temporal headache, dysarthria, and dysphagia. On examination, he had a right hypoglossal nerve palsy. The diagnosis of right internal carotid artery dissection was suggested by magnetic resonance imaging and confirmed by carotid angiography. A dynamic computed tomogram demonstrated enlargement of the carotid artery. In carotid dissection, the hypoglossal nerve may be compromised by local factors as it passes close to the carotid artery in the neck.
Adult↗
Membranous glomerulonephritis and Landry-Guillain-Barre syndrome.
Two cases of idiopathic membranous glomerulonephritis associated with acute inflammatory demyelinating polyradiculoneuropathy (Landry-Guillian-Barre syndrome) are described. In both of the patients, the onset of the nephrotic syndrome coincided with the development of severe ascending sensorimotor neuropathy. Although this association has previously been reported in four other isolated cases, it is not generally recognized by nephrologists and may be of significance in the future understanding of the immunopathogenesis of both diseases.
Aged↗