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)

The case of a 35-year-old man with a borderline-type cystosarcoma phyllodes is presented. Four years after the primary excision of the tumor, wide excision of a local recurrence and postoperative radiotherapy were performed. No repeated relapse was observed during a 5-year follow-up. Neither significant endocrine changes nor genetic alteration could be proven. However, a slightly increased SHBG concentration was detected, resulting in a decreased biologically available androgen level reduced testosterone/SHBG index. This phenomenon might be a consequence of the chronic liver disease of the patient due to his type II diabetes mellitus and alcohol abuse. In addition to the conventional histopathological examinations, immunohistochemical and electron-microscopic investigations were carried out on tissue sections, and the steroid receptors, EGF receptors and EGF-like activity of the tumor were also studied.
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PMID:Recurrent phyllodes tumor in a man. 952 Oct 24

Islet amyloidosis is characterized by the deposition and accumulation of amylin in pancreatic beta-cells and is observed in 90% of patients with type 2 diabetes. Previous studies have also revealed the presence of the specific heparan sulfate proteoglycan, perlecan, colocalized to islet amyloid deposits, similar to perlecan's known involvement with other amyloid proteins. In the present study, perlecan purified from the Engelbreth-Holm-Swarm (EHS) tumor was used to define perlecan's interactions with amylin (i.e., islet amyloid polypeptide) and its effects on amylin fibril formation. Using a solid phase-binding immunoassay, human amylin, but not rat amylin, bound immobilized EHS perlecan with a single dissociation constant (Kd) = 2.75 x 10(-6) mol/l. The binding of human amylin to perlecan was similarly observed using perlecan heparan sulfate glycosaminoglycans (GAGs), and was completely abolished by 10 micromol/l heparin. Using thioflavin T fluorometry, Congo red staining, and electron microscopy methodology, intact perlecan was found to enhance amylin fibril formation in a dosage-dependent manner, with the majority of these effects attributed to the heparan sulfate GAG chains of perlecan. Other sulfated GAGs and related macromolecules were also effective in the enhancement of amylin fibril formation in the order of heparin > heparan sulfate > chondroitin-4-sulfate = dermatan sulfate = dextran sulfate > pentosan polysulfate, implicating the importance of the specific GAG/carbohydrate backbone. The sulfate content of heparin/heparan sulfate was also important for the enhancement of amylin fibril formation in the order of heparin > N-desulfated N-acetylated heparin > completely desulfated N-sulfated heparin > completely desulfated N-acetylated heparin. These studies suggest that the enhancement effects of perlecan on amylin fibril formation are mediated primarily by both specific GAG chain backbone and GAG sulfate content, and implicate perlecan as an important macromolecule that is likely involved in the pathogenesis of islet amyloidosis.
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PMID:Sulfate content and specific glycosaminoglycan backbone of perlecan are critical for perlecan's enhancement of islet amyloid polypeptide (amylin) fibril formation. 956 95

Both epidemiological and experimental studies have shown that physical exercise deserves particular attention in any consideration of approaches to the prevention of neoplasia, especially since it also exerts consistent beneficial effects on the other major chronic diseases prevalent in the Western world, atherosclerosis and non-insulin dependent diabetes mellitus (NIDDM). The organ sites for which strong evidence has been gained for a protective influence of exercise or an elevated risk with a sedentary existence include the colon, prostate, breast and endometrium. The underlying mechanisms appear to centre on the hormones insulin and oestrogen, serum elevation of both of these endocrine factors being associated with increased risk of neoplastic development. The immense potential benefit of an increased level of exercise in the general population suggests that commensurate measures should be taken in the field of cancer education.
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PMID:Physical exercise: a pillar for cancer prevention? 969 26

Recent epidemiological evidence points to a link between non-insulin dependent diabetes mellitus type II (NIDDM) and cancer of the colon, liver, pancreas, breast and endometrium. This appears to be due to the long period of hyperinsulinaemia which precedes the clinical phase of NIDDM, insulin promoting colon tumour development as well as acting as a hepatocarcinogen. Indeed, the hormone could play a central role in neoplasia, and its influence could explain the observed enhancing effects of obesity and a high fat diet, as well as the inhibition associated with physical exercise, dehydroepiandrosterone administration and high soluble fibre intake. Measures to decrease insulin levels, including lifestyle improvement and supplementation with agents known to decrease insulin resistance may therefore offer a general approach to prevention of cancer in a wide variety of organ sites of major clinical importance.
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PMID:Implications of the hyperinsulinaemia-diabetes-cancer link for preventive efforts. 981 71

Levels of estradiol and progesterone from blood together with oestrogen (ER) and progesterone receptors (PgR) from breast tissue were studied from a total of 2500 data bank cases of breast neoplastic disease. We report here, 340 premenopausal women with recorded menstrual cycle data which enabled the study of the effect of peripheral hormone variation on ER and PgR with respect to cycle phase. The findings were also correlated with 30 immunohistochemical specimens. In the specimens with benign neoplasm (141 cases, age 28 +/- 18 years) the ER levels were low (9.2+/-9.4 fmol/mg protein) as in normal breast tissue, whereas PgR levels were high ( 76+/-102.4 fmol/mg protein). Both ER and PgR levels decreased in association with the peak of blood progesterone of the early secretory phase. In the 15 cases of benign neoplasm from the luteinic phase studied by immunohistochemistry there were few ER positive cells (29+/-15%) which were small (265+/-27 pixels) and faintly stained (MOD: 34+/-3UA), while the PgR positive cells were more numerous (79+/-15%), bigger (377+/-70 pixels), strongly stained (MOD: 48+/-5UA), and centrally located in the breast ducts. The differences in size and optical density were statistically significant indicating that both receptors are expressed by different cells. The cell cycle dependence of these differences is discussed. In the series of malignant neoplasms (199 cases, age 41+/-6 years), ER and PgR cytosol levels were both generally high (ER: 38+/-75.9, PgR: 86.6+/-137), and did not show variations due to the menstrual cycle, while blood progesterone, PgR, and the percentage of ER positive cases increased during the menstrual cycle. The 15 malignant cases in the luteinic phase showed, through immunohistochemistry, that size and staining intensities of receptor positive cells were similar to the other 199 cases and were not found to be directly influenced by hormonal activity related to the menstrual cycle. Comparisons between benign and malignant specimens showed significant biochemical and immunohistochemical differences in the degree of ER positivity while, on the contrary, PgR levels were similar.
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PMID:Estradiol, progesterone and steroid receptors. Benign cycling versus malignant non cycling cells. 1035 70

The fundamental clinical features of PCOS include hirsutism and menstrual irregularities from the time of menarche. Obesity is present in approximately 50% of these patients, some of whom also carry a diagnosis of NIDDM. The biochemical abnormalities associated with the clinical picture include LH hypersecretion, hyperandrogenism, acyclic estrogen production, subnormal SHBG levels, and hyperinsulinemia. Hirsutism usually progresses slowly in patients with PCOS; however, the clinical presentation can resemble virilizing tumors, late-onset CAH, or Cushing syndrome. Virilization or rapidly progressive hirsutism requires immediate investigation to rule out a virilizing tumor. Goals of therapy for teenage patients include decreasing levels of bioavailable androgen, blockade of androgen action at target tissues, stabilization of the endometrium, and reduction of insulin resistance. Although the original description of PCOS by Stein and Leventhal was published in 1935, the cause of PCOS remains unknown. This reason, coupled with the fact that PCOS-related insulin resistance is an important cause of NIDDM in women, has caused this disorder to become one of interest and active investigation. Future research will likely be able to delineate mechanisms behind the defects of carbohydrate metabolism and ascertain large multigeneration kindreds for linkage analyses to identify affected genes. Future studies are also likely to confirm whether young women with PCOS are at increased risk for cardiovascular disease and other long-term health complications. As new pathophysiologic mechanisms are identified, the promise of new therapies arises, including treatments that could potentially reduce the long-term incidence of adverse health consequences.
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PMID:Menstrual disorders in adolescents. Excess androgens and the polycystic ovary syndrome. 1038 5

Type 2 diabetes mellitus is a common disabling disease with onset in middle-aged individuals, caused by an imbalance between insulin production and action. Genetic studies point to major genetic components, but, with the exception of maturity-onset diabetes of the young (MODY), specific diabetes susceptibility genes remain to be identified. Recent studies showed that a dominant negative mutation in the insulin promoter factor-1 (IPF-1), a pancreatic beta-cell specific transcription factor, causes pancreatic agenesis and MODY. Thus, we investigated 192 French, non-MODY type 2 diabetic families for mutations in IPF-1. We identified 3 novel IPF-1 mutations, including 2 substitutions (Q59L and D76N) and an in-frame proline insertion (InsCCG243). Functional transactivation assays of these IPF-1 mutant isoforms in a beta-pancreatic tumor cell line transfected with a transcriptional reporter and IPF-1 expression plasmids demonstrate a significant inhibition of basal insulin promoter activity (stronger with the InsCCG243 mutant). We find that the InsCCG243 mutation is linked, in 2 families, to an autosomal dominant-like late-onset form of type 2 diabetes, in which insulin secretion becomes progressively impaired. The lower penetrance D76N and Q59L mutations were more prevalent and were associated with a relative risk of 12.6 for diabetes and with decreased glucose-stimulated insulin-secretion in nondiabetic subjects. We propose that IPF-1 mutations can cause MODY or apparently monogenic late-onset diabetes and that they represent a significant risk factor for type 2 diabetes in humans.
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PMID:Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus. 1054 31

Classic Cushing's syndrome is a rare disease with an estimated incidence of 1 case per 100,000 persons. With routine use of imaging techniques such as ultrasound and CT, adrenal masses are being detected with increased frequency. A substantial percentage of these incidentalomas are hormonally active, with 5% to 20% of the tumors producing glucocorticoids. Autonomous glucocorticoid production without specific signs and symptoms of Cushing's syndrome is termed subclinical Cushing's syndrome. With an estimated prevalence of 79 cases per 100,000 persons, subclinical Cushing's syndrome is much more common than classic Cushing's syndrome. Depending on the amounts of glucocorticoids secreted by the tumor, the clinical spectrum ranges from slightly attenuated diurnal cortisol rhythm to complete atrophy of the contralateral adrenal gland with lasting adrenal insufficiency after unilateral adrenalectomy. Patients with subclinical Cushing's syndrome lack the classical stigmata of hypercortisolism but have a high prevalence of obesity, hypertension, and type 2 diabetes. All patients with incidentally detected adrenal masses scheduled for surgery must undergo testing for subclinical Cushing's syndrome to avoid postoperative adrenal crisis. The best screening test to uncover autonomous cortisol secretion is the short dexamethasone suppression test. Because the adrenal origin of a pathologic cortisol secretion is anticipated, the author prefers a higher dexamethasone dose (3 mg instead of 1 mg) to reduce false-positive results. A suppressed serum cortisol level of less than 3 micrograms/dL (80 nmol/L) after dexamethasone excludes significant cortisol secretion by the tumor. A serum cortisol level greater than 3 micrograms/dL requires further investigation, including confirmation by high-dose dexamethasone (8 mg) suppression testing, a CRH test, and analysis of diurnal rhythm. Determination of urinary free cortisol is less useful because increased values are a late finding usually associated with emerging clinical signs of Cushing's syndrome. Patients with suppressed plasma ACTH in response to CRH generally have adrenal insufficiency after surgery and require adequate perioperative and postoperative substitution therapy. Whether patients with subclinical Cushing's syndrome should undergo adrenalectomy is a matter of debate. The author performs surgery in young patients (< 50 years), in patients with suppressed plasma ACTH, and in patients with a recent history of weight gain, substantial obesity, arterial hypertension, diabetes mellitus, and osteopenia. In completely asymptomatic patients with normal plasma ACTH concentrations and in patients older than 75 years, the author recommends a nonsurgical approach. A large prospective randomized study is necessary to evaluate the benefits of surgery versus conservative treatment in patients with subclinical Cushing's syndrome.
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PMID:Subclinical Cushing's syndrome. 1073 63

Although an association between diabetes and cancer was found over 100 years ago, the issue underwent different interpretations over the subsequent decades, and only modern, prospective, epidemiological cohort and case-control studies conducted in several countries have provided reliable evidence of an increased cancer risk in diabetic patients, mainly in those with type 2 diabetes. This risk varies according to the tumor site: it is the greatest for primary liver cancer, moderately elevated for pancreatic cancer, and relatively low for colorectal, endometrial, breast, and renal cancers. The cause of the association is not clear and remains the subject of different hypotheses. The most frequently cited reason is the potential effect of insulin. Found in high concentrations, due to insulin resistance in most patients with type 2 diabetes, this hormone is believed to express a mitogenic effect. This hypothesis needs to be confirmed in appropriately programmed prospective studies, but it may already be helpful in choosing an adequate treatment for type 2 diabetes to achieve optimal metabolic control with a simultaneous reduction in hyperinsulinemia, such as diet, physical exercise, metformin, and acarbose.
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PMID:Diabetes mellitus and cancer. 1102 48

We report on a 33-year-old patient from Sri Lanka who had been suffering from recurrent episodes of abdominal cramps since he was ten years old. He additionally suffered from postprandial flatulence and an increased frequency of bowel movements. By the age of 24, his condition had worsened with polyuria and polydipsia and he was diagnosed with type II diabetes mellitus. Recently, the patient's compliance deteriorated steadily and his diabetes mellitus was uncontrolled. His flatulence continued and he had six to seven bowel movements daily. He presented to us with renewed bouts of severe stomach cramps, similar to the painful episodes that the patient experienced in his youth. After exclusion of other etiologies and judging by the clinical picture, the patient's origin and the sonographically and radiologically verified pancreatic calcification, we rendered the diagnosis of a tropic calcifying pancreatitis with secondary diabetes mellitus. According to the literature, malignant neoplasia may develop on the basis of this disease. However, we were able to rule out a carcinoma as the cause of the current pain episodes in this patient based on clinical findings and course. We attributed the stomach cramps to compression of the common bile duct by the fibrotic head of pancreas. Pain and cholestasis regressed, thus obviating the need for surgical intervention (pancreaticojejunostomy). On therapy with enzyme substitution and insulin, the patient's exo- and endocrine pancreatic insufficiency was asymptomatic.
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PMID:[Chronic abdominal pain in a young diabetic patient]. 1111 10


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