Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor binding proteins interfere in the IGF-I and -II radioimmunoassays. In an attempt to overcome this problem, we have compared the use of truncated IGF-I, with reduced IGFBP affinity, and IGF-I as radioligands for IGF-I RIA measurements in serum separated by acid gel filtration or acid ethanol extraction followed by cryo-precipitation. With truncated IGF-I as radioligand the IGF-I measurements in acid gel filtrates and acid ethanol extracts were significantly correlated in healthy subjects (N = 42, r = 0.91, p less than 0.001) and in patients with acromegaly (N = 10, r = 0.85, p less than 0.01), GH deficiency (N = 10, r = 0.88, p less than 0.001) or Type I diabetes mellitus (N = 10, r = 0.90, p less than 0.001). In contrast, the IGF-I concentrations in acid ethanol extracts determined with IGF-I as radioligand did not correlate with those in acid gel filtrates using truncated IGF-I radioligand in patients with acromegaly (r = 0.61, NS) or GH deficiency (r = 0.46, NS). In the latter group the mean IGF-I concentrations measured in acid ethanol extracts were erroneously elevated by 112%. Low-affinity antibodies used for IGF-II RIA determinations failed to give reliable results in acid ethanol extracts from patients with Type I diabetes mellitus or GH deficiency. In conclusion, erroneously high IGF-I concentrations owing to binding of the radioligand to IGFBPs not completely removed by acid ethanol extraction can be avoided by the use of truncated IGF-I as radioligand.
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PMID:Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays: improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand. 206 92

Osteocalcin, non-collagenous vitamin K dependent bone protein is as a biochemical indicator of osteoblastic activity and metabolic turnover in bone, valuable in the diagnosis of several diseases and in investigations of the dynamics of osseous changes (processes) during treatment of osteopathies. Elevated osteocalcin levels are normal in childhood and adolescence. In the diurnal rhythm the peak is recorded in the early hours. Pathologically elevated values are associated with primary hyperparathyroidism, Paget's disease, chronic renal failure, acromegaly and some malignities. A rise in women during the early postmenopausal period signalizes an enhanced metabolic turnover of bone in those women who are candidates of postmenopausal osteoporosis. Low levels are as a rule recorded in advanced age, in nanism, hypoparathyroidism, type 1 diabetes, rheumatoid arthritis, vitamin D deficiency, vitamin K deficiency, hypercorticalism and glucocorticoid treatment.
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PMID:[Osteocalcin]. 227 72

It is well known that muscarinic cholinergic blockade either reduces or abolishes stimulated GH release in normal subjects. In this study we have investigated whether cholinergic muscarinic blockade could reduce the GH responses to GRF 1-29 and TRH in acromegalic subjects. Eight acromegalic subjects underwent two GRF tests (GRF 1-29, 1 microgram/kg i.v.) with and without pirenzepine (0.6 mg/kg, i.v.). A further four of these patients received TRH (200 micrograms/kg, i.v.) on separate occasions with and without pirenzepine (0.6 mg/kg, i.v.). Cholinergic muscarinic blockade did not alter the GH responses to GRF and TRH in patients with acromegaly. These findings are in contrast with previous data reported on the effects of cholinergic blockade on stimulated GH levels in normal subjects and in patients with type I diabetes mellitus and are compatible with the view that somatotroph adenomas are functionally disconnected from hypothalamic control mechanisms.
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PMID:Lack of effect of muscarinic cholinergic blockade on the GH responses to GRF 1-29 and TRH in acromegalic subjects. 287 6

17 patients with active acromegaly (7 of them had diabetes mellitus, too), 13 patients with type I diabetes mellitus and 20 healthy controls were examined. The residual beta-cell secretion was determined by venous Tolbutamide test and the insulin sensitivity was determined by euglycemic clamp-technique. A positive correlation was found between the growth hormone level and prolactin and the size of the basic insulin secretion. In acromegaly (with or without diabetes) the sensitivity of beta-cell apparatus towards the stimulant Tolbutamide is preserved but the insulin reserves are diminished. There exists a positive correlation between the growth hormone level and the degree of insulin resistance and between the increased prolactin level and the degree of insulin resistance in acromegalic patients.
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PMID:[Insulin secretion and action in acromegaly]. 332 80

The response of growth hormone, cortisol, and catecholamines to hypoglycaemia produced by a continuous intravenous infusion of insulin was investigated in 10 normal subjects and 15 patients with pituitary disease. The insulin infusion rate was started at 2 U/hour for adolescents, 4 U/hour for adults, and 6 U/hour for patients with acromegaly. If required the rate was increased during the test depending on changes in blood glucose, measured by a Reflomat with low reading glucose oxidase strips. Stopping the infusion when the blood glucose concentration had fallen to 2.0 mmol/l (36 mg/100 ml) resulted in a maximum further fall of 0.7 mmol/l (13 mg/100 ml) and a subsequent spontaneous rise in blood glucose concentration. The rise was identical in normal subjects and in patients with hypopituitarism, further evidence that pituitary hormones--in contrast to glucagon and catecholamines--are relatively unimportant in the recovery from hypoglycaemia. The only patient who required intravenous glucose to restore normoglycaemia was a patient with longstanding insulin dependent diabetes. A comparison with the conventional bolus injection test showed that continuous intravenous insulin infusion was more reliable in producing adequate but not excessive hypoglycaemia and the hormone responses were equivalent. The continuous intravenous insulin infusion may offer particular advantages in the investigation of growth hormone deficiency.
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PMID:Testing the anterior pituitary: hypoglycaemia produced by continuous intravenous insulin infusion. 641 Dec 30

Diabetes mellitus is a frequent manifestation in patients with acromegaly and it can show up even before the latter manifests. Typically, the diabetes mellitus in these patients does not tend to develop ketosis. We present the case of a patient hospitalized due to diabetic ketoacidosis associated to a perianal abscess. Diabetes mellitus type I was rejected and the presence of insulin-resistance was verified. She required insulin therapy just for three months. The clinical, hormonal and radiological evaluation showed, three years latter, the presence of a hypophyseal tumor producing growth hormone. After performing a trans-sphenoidal adenomectomy, the insulin-therapy could be removed with a normal glycemic profile. This case of acromegaly demonstrates the relationship between growth hormone and glucose metabolism. It can be considered that the ketoacidosis was the first manifestation of the acromegaly, which is exceptional.
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PMID:[Diabetic ketoacidosis as the first manifestation of acromegaly]. 774 14

The pertinent literature on the prevalence, clinical manifestations and pathogenic mechanisms of sleep apnoea (SA) in endocrine diseases, namely acromegaly, Cushing syndrome, hypothyroidism and diabetes mellitus was reviewed. An increased prevalence is well documented in patients with active and treated acromegaly. While most authors report peripheral obstruction, due to hypertrophy of tongue and pharyngeal tissues, to be the cause of SA in acromegaly, some findings argue for a role of hormone-induced changes of central respiratory control. SA is also more common in hypothyroidism, especially when myxedema is present. The associated edema and myopathy appear to be of pathogenic importance. Thyroxin substitution is frequently effective for the treatment of SA but nCPAP can be necessary initially and in some patients even after remission of clinical signs of hypothyroidism. In Cushing disease and syndrome, parapharyngeal fat accumulation can cause SA, but no epidemiological information is available. In non insulin dependent diabetes (NIDDM), obesity is the common risk factor for both, nocturnal hypoxia and insulin resistance. In IDDM, the development of autonomic neuropathy may predispose to SA. Where treatment of the underlying endocrine disease is unable cure the associated SA, nCPAP is usually the treatment of first choice. More prospective studies are clearly needed to establish prevalences and resolve the controversies regarding pathogenesis.
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PMID:Sleep apnoea in endocrine diseases. 961 23

At present, the circulating bioactivity of insulin-like growth factor I (IGF-I) is estimated by immunological measurements of IGF-I levels. However, immunoassays ignore the modifying effects of the IGF-binding proteins (IGFBPs) on the interaction between IGF-I and the IGF-I receptor (IGF-IR). Therefore, we developed an IGF-I kinase receptor activation assay (KIRA) based on cells transfected with the human IGF-IR gene. The bioassay was sensitive (detection limit 0.08 microg/l), specific (cross-reactivity of insulin, insulin analogs, and proinsulin was <1%; IGF-II cross-reactivity was 12%), and accurate (within- and between-assay coefficients of variation <7 and <15%). The operational range of the assay (0.25-10.0 microg/l) allowed for determination of IGF-I bioactivity in serum from patients with, for example, growth hormone deficiency, type 1 diabetes, and acromegaly. Addition of IGFBPs dose dependently reduced the KIRA signal, whereas addition of IGF-II to preformed complexes (1:1 molar ratio) of IGF-I and IGFBP dose dependently increased IGF-I bioactivity by displacement of bound IGF-I. In conclusion, the KIRA will enable us to compare IGF-I bioactivity with existing immunological measurements of IGF-I in serum and, hopefully, to elucidate the factors that determine IGF-I bioactivity in vivo.
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PMID:A highly sensitive and specific assay for determination of IGF-I bioactivity in human serum. 1260 4

GH hypersecretory states include organic and functional causes. Among functional GH hypersecretory states, enhanced somatotroph secretion physiologically occurs at birth associated with reduced IGF-I levels reflecting the still immature sensitivity of liver to circulating GH levels; this may also occur in women exposed to oral extrogens. Pathophysiological conditions of GH hypersecretion are generally associated with congenital or acquired/functional conditions of peripheral GH insensitivity. Genetic alterations of the GH receptor lead to the so called Laron's syndrome. On the other hand, a relevant number of clinical conditions (malnutrition, malabsorption, anorexia nervosa, liver cirrhosis, renal failure, Type 1 diabetes mellitus) are associated with acquired GH insensitivity and a more or less pronounced GH hypersecretion. Both organic and acquired conditions of GH insensitivity show low IGF-I synthesis and release and therefore lack the negative IGF-I feedback action on somatotroph function. GH hypersecretion may be associated with renal failure; however, in this case, the alteration in the metabolic clearance rate of GH would also have a role; moreover, IGF-I levels are generally normal in this condition. Hyperthyroidism is another condition connoted by elevated GH levels that reflects a true GH hypersecretory state and is, in fact, associated with high-normal IGF-I levels; this peculiar condition is likely to be reflecting the stimulatory effect of thyroid hormones on both GH and IGF-I secretion and is promptly reversed by treatment-induced euthyroidism. Apart from these "functional" hypersecretory state, the classic organic GH hypersecretory state is represented by acromegaly or giantism. In these conditions GH hypersecretion is generally sustained by a pituitary adenoma hypersecreting GH alone or together with another pituitary hormone, mostly PRL; less frequently GH hypersecretion may be due to ectopic GHRH hypersection. Exaggerated GH secretion elicits exaggerated IGF-I synthesis and secretion that is, in turn, responsible for the large majority of endocrine signs and symptoms. In the appropriate clinical context of acromegalic features, evidence of concomitant marked GH and IGF-I hypersecretion at baseline demonstrates active acromegaly or giantism and indicates the need for magnetic resonance imaging in order to verify the presence of a pituitary tumor. However, as random measurement of basal GH levels is not reliable for definite diagnosis of acromegaly, it is considered mandatory to rely on the lack of GH suppression below 1 microg/l during oral glucose tolerance test (OGTT) coupled with elevated IGF-I levels. The same criteria are assumed, at present, to define true cure of the disease after (or under) treatment. There is consensus about the assumption that concomitant normalization or persistent abnormality of both OGTT-induced GH nadir and IGF-I levels define a successfully or a poorly controlled disease status, respectively. On the other hand, acromegalic patients with GH nadir above 1 microg/l or IGF-I levels persistently elevated are inadequately controlled and their disease should not be considered inactive. It has been clearly demonstrated that an extended exposure to GH and IGF-I excess level, even if slight, has a very harmful effect on patients; therefore early diagnosis of acromegaly and appropriate definition of its cure are of fundamental extreme in order to plan a prompt and appropriate therapeutic intervention(s) guaranteed also by the continuous improvement in the therapeutic tools available to treat this systemic disease.
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PMID:Hormonal diagnosis of GH hypersecretory states. 1549 57

We report a rare case of type 1 diabetes in a woman associated with acromegaly who was treated with surgery after pregnancy. An 18-year-old woman came to our hospital in April, 1998, complaining of thirst, polydipsia, polyuria, appetite loss, body weight loss of 8 kg in a month, and amenorrhea beginning 2 months earlier. Based on laboratory data, she was diagnosed as having type 1 diabetes mellitus. Although we suspected her of having acromegaly because of high growth hormone (GH) levels (6.9 or 8.5 ng/ml), blood levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) were within normal range and the circadian rhythm of her blood GH levels was normally maintained. Her blood GH level was elevated to 12.6 ng/ml 15 minutes after a TRH administration. Blood GH levels were suppressed from 49 ng/ml to 1.5 ng/ml 4 hours after an oral administration of 2.5 mg of bromocriptine. A magnetic resonance images (MRIs) showed pituitary swelling, but no nodules were found in the pituitary. Therefore, we diagnosed her as having acromegaly and observed her without surgery, while prescribing diet therapy and intensive insulin therapy for diabetes. We started a treatment of oral administration of 7.5 mg of bromocriptine per day for the acromegaly from April 28, 2000, because her elevated GH was suspected of causing her diabetes to be poorly controlled. During a pregnancy from October, 2000 to September, 2001, diabetic control was improved with increased administration of insulin under a constant dose of bromocriptine. She delivered a normal full-term infant. After the bromocriptine therapy was stopped as she hoped to breastfeed, blood levels of GH and IGF-1 became elevated and her diabetic control deteriorated. As her pituitary tumor observed in pituitary MRIs became larger during the course, a transsphenoidal surgery was performed on March 8, 2002. After the surgery, blood levels of GH and IGF-1 lowered and diabetic control improved again. We concluded as follows: to rule out acromegaly in patients with poorly controlled diabetes, 1) measurements of serum GH and IGF-1 should be performed, and 2) pituitary MRIs should be performed if blood levels of GH or IGF-1 are high.
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PMID:Type 1 diabetes associated with asymptomatic acromegaly successfully treated with surgery after pregnancy: a case report. 1612 8


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