Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten acromegalic patients, four previously untreated, were studied before and at regular intervals during treatment with the long-acting somatostatin analog SMS 201-995 (200-300 micrograms daily for 2 or 3 sc injections for 16-108 weeks). All patients had rapid clinical improvement, with disappearance of excessive perspiration, paresthesias, and headache within the first 6 weeks of therapy. The mean 24-h serum GH concentrations fell from 44.0 +/- 7.8 (+/-SE) micrograms/L before to 5.9 +/- 1.0 microgram/L at the end of therapy. The GH levels from 2-6 h after the acute administration of 50 micrograms SMS 201-995 before the start of therapy correlated significantly with the mean 24-h GH concentrations after 16-108 weeks of treatment (P less than 0.05). The initially increased serum somatomedin-C (Sm-C) levels normalized in 5 of these 10 patients; the mean values were 7.3 +/- 0.9 U/mL before and 2.9 +/- 0.7 U/mL at the end of therapy. The Sm-C and mean GH levels continuously decreased during long term therapy; the concentrations after 1.5-2 yr of therapy were significantly lower than those after 6-12 months of therapy (P less than 0.01 and P less than 0.01, respectively). A slight decrease in the size of the pituitary tumor was noted by computed tomography in three of six patients. Transient clinically detectable steatorrhea occurred in two patients. Postprandial hyperglycemia occurred during therapy in eight patients, while in two patients with type 2 diabetes mellitus carbohydrate tolerance improved in one and deteriorated in the other. SMS 201-995 is a highly effective medical treatment for acromegaly. Clinically improvement occurs rapidly, and the inhibition of serum GH and Sm-C levels persisted even after more than 1 yr of therapy. No important subjective side-effects were noted. SMS 201-995 is an excellent drug in patients in whom acromegaly persists after surgery and for interim treatment to shorten the period of clinical activity after irradiation.
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PMID:SMS 201-995 induces a continuous decline in circulating growth hormone and somatomedin-C levels during therapy of acromegalic patients for over two years. 288 85

The responses of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) to oral administration of L-dopa were studied in normal subjects and patients with various endocrine and metabolic diseases to clarify the pathophysiological role of the GHRH-GH axis. In normal subjects, the plasma GHRH concentration was increased from the basal value of 9.8 +/- 1.4 pg/ml (mean +/- SE) to 34.8 +/- 3.1 pg/ml at 30 approximately 90 min after oral administration of 500 mg L-dopa, followed by a rise of GH release (plasma GH level from less than 1 ng/ml to 21.7 +/- 4.7 ng/ml) in most cases, indicating that L-dopa stimulates GH secretion via hypothalamic GHRH. On L-dopa administration, no apparent increases in both plasma GHRH and GH concentrations were observed in patients with hypothalamic hypopituitarism, whereas GHRH administration induced almost normal GH response. In patients with acromegaly, the plasma levels of GHRH remained stationary after the L-dopa administration and did not correlate with plasma GH levels. In subjects with simple obesity, the responses of plasma GHRH (peak 13.2 +/- 1.2 pg/ml) and GH (peak 4.3 +/- 1.7 ng/ml) to L-dopa were significantly lower than those in normal subjects (p less than 0.01). In patients with primary hypothyroidism, peak levels of plasma GHRH (12.6 +/- 1.3 pg/ml) and GH (2.4 +/- 0.6 ng/ml) were significantly lower than those in normal subjects (p less than 0.01). In patients with non-insulin dependent diabetes mellitus (NIDDM), the responses of GHRH and GH were divided into 2 groups; in the responder the peak values of GHRH and GH were 19.4 +/- 8.6 pg/ml and 12.2 +/- 1.4 ng/ml and in the low or non responder 14.7 +/- 1.5 pg/ml and 2.0 +/- 0.6 ng/ml, respectively. Between both groups, there was a significant difference in the values of fasting blood sugar and HbA1 and mean suffering period. These findings suggest that GH secretion evoked by the L-dopa administration is induced by GHRH released from the hypothalamus, and impairment of GH secretion associated with simple obesity, primary hypothyroidism, or NIDDM may be in part attributed to insufficiency of GHRH release from the hypothalamus, and indicate that L-dopa test is clinically useful for evaluating the ability of intrinsic GHRH release in such diseased states.
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PMID:[Effect of oral administration of L-dopa on the plasma levels of growth hormone-releasing hormone (GHRH) in normal subjects and patients with various endocrine and metabolic diseases]. 312 83

Utilizing an acid gel chromatography and insulin radioreceptor assay (RRA), serum levels of receptor assayable insulin-like activities were measured under various conditions. Acid gel filtration of sera on a Sephadex G-50 was adopted to separate small molecular ILAs from binding proteins before the assay by RRA. By employing 125I-pork insulin as the tracer, and pork insulin as the standard, an RRA for insulin was developed, in which kidneys of sacrificed pregnant guinea pigs were used as the source of the solubilized receptor. After gel-filtration of the sera, pooled fractions, which grossly corresponded to those of 125I-insulin marker, were assayed by RRA. The subjects consisted of fifty-nine cases: normal control subjects (n = 19), active acromegaly (6), Sheehan's syndrome (5), liver cirrhosis (7), chronic renal failure (10), non-insulin dependent diabetes mellitus (6), overt hyperthyroidism (5) and Nelson's syndrome (1). The average receptor assayable ILA of the normal control subjects was 40.2 +/- 12.2 ng/ml. As insulin RRA has a big interassay variation, receptor assayable ILA-ratio was used to minimize the variation, and each data was shown as the ratio to the average ILA of the normal controls. By this method, sera from normal adults had a mean (+/- SD) receptor assayable ILA ratio of 1.00 +/- 0.28. Four out of six cases of acromegaly revealed significantly high concentrations, and the average receptor assayable ILA-ratio of acromegaly was 1.30 +/- 0.28 (mean +/- SD, p less than 0.015). In the cases of Sheehan's syndrome, the ILA-ratio was 0.30 +/- 0.12, which was significantly low (p less than 0.001). Therefore, GH dependency was suspected from these two factors. However, the direct correlation was not indicated between GH and receptor assayable ILA. It was also considered that receptor assayable ILA was influenced not only by GH but also by some other factors. Furthermore, the subjects with liver cirrhosis indicated the low levels of receptor assayable ILA-ratio of 0.46 +/- 0.31, while the subjects with chronic renal failure showed the high ILA-ratio of 1.59 +/- 0.45 (p less than 0.05). No differences in ILA-ratio were found in the subjects with diabetes mellitus, hyperthyroidism and Nelson's syndrome, compared to the normal subjects.
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PMID:[Serum levels of receptor assayable insulin-like activity in various diseases]. 636 8

Exaggerated growth hormone (GH) responses to various provocative stimuli have been reported previously in insulin-dependent diabetes mellitus (IDDM). Little is known about GH response to synthetic gonadotropin-releasing hormone (GnRH) in diabetes. It has been reported to be exaggerated in active acromegaly. We investigated GH, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels after GnRH administration in seven IDDM and eight non-insulin-dependent diabetic (NIDDM) patients. They were poorly controlled from a metabolic point of view. Ten healthy subjects served as the control group. FSH and LH levels increased significantly after GnRH in all groups. In contrast, GnRH did not elicit significant GH increments above baseline levels in any group. Moreover, mean areas under the GH curves were comparable among the three groups. These results suggest that poorly controlled IDDM and NIDDM does not lead to inappropriate GH responses to GnRH.
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PMID:Does gonadotropin-releasing hormone administration affect serum growth hormone levels in poorly controlled insulin-dependent and non-insulin-dependent diabetes mellitus? 759 3

A 58-year-old woman was admitted to our hospital for impaired consciousness, hyperglycemia and bitemporal hemianopsia. She was diagnosed as having NIDDM one year ago and was treated with diet and glibenclamide (1.25 mg/day) for 6 months. However, she stopped her medical treatment one month ago and then polydipsia and general fatigue were manifested. She was admitted to a hospital five days ago at which time hyperglycemia (405 mg/dl) and anemia (Hb8.0g/dl) were detected. She was transferred to our hospital for control of blood glucose and further examination of bitemporal hemianopsia. She showed typical acromegalic features including enlargement of the nose, lips and tongue, increased heel pad and acral growth. Conscious disturbance was cured by the infusion of saline and the administration of insulin. Endoscopy revealed an active gastric ulcer (A1). Endocrine data disclosed increased GH levels in plasma and urine, whereas plasma IGF-1 levels were low. Plasma GH paradoxically increased following the administration of TRH. A water deprivation test showed an impaired increase in urinary osmolarity, indicating partial central diabetes insipidus (DI). MRI with Gd-contrast revealed a macroadenoma which progressed toward suprasella. She was diagnosed as having acromegaly, partial DI and probable hyperosmolar hyperglycemic nonketotic diabetic pre-coma. Polyuria (5-101/day) due to partial DI was controlled by the administration of DDAVP (10 micrograms/day). The constant subcutaneous administration of octreotide (240 micrograms/day) resulted in normal plasma GH levels and a marked shrinkage of the pituitary tumor. The pituitary tumor was finally removed by the transsphenoidal approach following treatment with octreotide for 4 months. HE staining of the pituitary tumor showed atrophic and acidophilic cells surrounded by hyaloid connective tissue. After the surgery, plasma GH levels were normalized and complications were cured. In conclusion, this is a very rare case of acromegaly associated with diabetic pre-coma and partial DI, and effectively treated with constant subcutaneous infusion of octreotide.
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PMID:[Effective treatment with constant subcutaneous infusion of octreotide in a patient with acromegaly associated with diabetic pre-coma and diabetes insipidus]. 785 21

A number of endocrine disorders are associated with varying degrees of glucose intolerance. Sustained hypersecretion of hormones with actions antagonistic to insulin (e.g., GH, glucocorticoidos, catecholamines, glucagon) or which interfere with insulin secretion (e.g., catecholamines, hypokalemia) is often associated. And so, acromegaly, Cushing's syndrome, pheochromocytoma, primary aldosteronism, hyperthyroidism, glucagonoma and others are included in endocrine-associated diabetes. The glucose intolerance occurring secondary to endocrine disorders is usually moderate degree and overt diabetes with symptomatic hyperglycemia is an uncommon event, unless an underlying genetic diabetic diathesis also present in the same individual. The small subgroup of acromegalics(5-10%) with severe glucose intolerance requiring insulin therapy have low endogenous insulin levels and insulin responses that are markedly impaired. It has been suggested that these patients are really true diabetics. These are patients with NIDDM. Retinal, renal and neurological complications are uncommon in patients with endocrine-associated diabetes.
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PMID:[Diabetes secondary to endocrinolopathies]. 891 32

The aim of our work was to study non-insulin-mediated glucose uptake (NIMGU), in the postabsorptive state, in several pathologies characterized by peripheral insulin resistance, namely, obesity (n = 10), NIDDM (n = 7), acromegaly (n = 7) and Cushing's disease (n = 6). These groups were compared with a group of 16 healthy subjects. To estimate peripheral insulin sensitivity (SI) and glucose effectiveness (SG), we used the minimal model of glucose metabolism. Although all of these pathologies showed severe insulin resistance (control: 6.44 +/- 2.63, obesity: 2.84 +/- 1.57, NIDDM: 1.71 +/- 0.77, acromegaly: 1.88 +/- 1.23, Cushing's disease: 1.87 +/- 0.66 x 10(-4) min-1 (microU/ml)-1, P < 0.01), fasting insulin-mediated glucose uptake (IMGU) did not differ significantly among the five groups, because reactive hyperinsulinaemia was present in all of these states. The contribution of NIMGU to whole-body glucose uptake did not differ significantly among the five groups (control: 77 +/- 8%; obesity: 77 +/- 9%; acromegaly: 82 +/- 8%; Cushing's disease: 83 +/- 8%; NIDDM: 84 +/- 7%). In conclusion, our data show that, in the postabsorptive period, non-insulin mediated glucose uptake is a major determinant of glucose disposal and is similar in the different pathologies studied; on the other hand, although absolute rates of basal insulin-mediated glucose uptake are reduced in insulin-resistant states, they did not achieve statistical value compared with control subjects because of compensatory hyperinsulinaemia.
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PMID:Non-insulin-mediated glucose uptake in several insulin-resistant states in the postabsortive period. 959 80

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

The soluble form of the insulin-like growth factor II/mannose 6-phosphate (IGF-II/M6-P) receptor has been detected in serum from a variety of mammalian species. We report the development of a highly sensitive quantitative human IGF-II/M6-P receptor immunoassay. Antibodies raised to receptor purified from a human hepatoma cell line by phosphomannan affinity chromatography were used to develop a specific enzyme-linked immunosorbent assay. In this assay, the serum level of soluble receptor for healthy adult subjects was 0.70 +/- 0.23 mg/L. We have shown that soluble receptor is developmentally regulated, with levels in infant (1.12 +/- 0.28 mg/L) and prepubertal (1.18 +/- 0.6 mg/L) subjects dropping by 40% during adolescence (0.73 +/- 0.61 mg/L) and remaining constant throughout adulthood. Further, the receptor is gestationally regulated, with a highly significant association between gestational age and maternal serum receptor levels (r = 0.947; P < 0.0001). Noninsulin-dependent diabetes mellitus (0.98 +/- 0.25 mg/L) and insulin-dependent diabetes mellitus (0.98 +/- 0.25 mg/L) mildly elevated soluble receptor levels, whereas end-stage renal failure (0.75 +/- 0.23 mg/L) and acromegaly (0.79 +/- 0.25 mg/L) did not affect receptor levels. Additionally, we have shown that soluble receptor is present in amniotic fluid, but at a 100-fold lower concentration than serum levels. The ability to quantitate soluble IGF-II/M6-P receptor levels in serum and other fluids provides a valuable tool that will help to further elucidate the role of the receptor in human physiology and disease states.
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PMID:Regulation of soluble insulin-like growth factor II/mannose 6-phosphate receptor in human serum: measurement by enzyme-linked immunosorbent assay. 1002 25

In a 69-year-old woman with a complicated history of multiple endocrine neoplasia type I (MEN 1), growth hormone overproduction was found without clinical features of acromegaly. Zollinger-Ellison syndrome was diagnosed at the age of 36 years. Total gastrectomy and partial pancreatectomy were performed. Two years later hypercalcaemia occurred, hyperparathyroidism was suspected and three hyperplastic parathyroid glands were removed. In 1994 the plasma gastrin level was elevated and a computerized tomography of the abdomen revealed a 1.5-cm large pancreatic tumour. Screening of the pituitary functions was unremarkable and a magnetic resonance scan of the pituitary gland showed no abnormalities. In 1995 type II diabetes mellitus was diagnosed. In 1997 basal plasma growth hormone levels were raised and plasma IGF-I levels were alternately high and normal. The patient had no clinical signs of acromegaly, but glucose tolerance testing resulted in a paradoxical rise in growth hormone concentration compatible with the diagnosis of growth hormone overproduction. Magnetic resonance imaging of the pituitary gland revealed a microadenoma.
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PMID:Growth hormone overproduction in a patient with multiple endocrine neoplasia type I. 1115 46


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