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)

Isolated hypoaldosteronism is found in 75% diabetics where the disease has persisted for 10 or more years. Sporadically it is found in congenital autonomous neuropathy, in acute glomerulonephritis, in gouty kidney, tubulointerstitial nephritis, after transplantation of the kidney, on mytomycin etc. During dynamic testing of the response of plasma renin activity and aldosterone to the administration of furosemide and a vertical position in diabetics a significantly reduced response was recorded as compared with non-diabetic hypertonic subjects. In 18.3% no response was observed (decompensated form of IHH). Diabetic hypertonics behaved like control hypertonics on long-term beta-blocker treatment. In the decompensated form of IHH after administration of drugs interfering with the activity of SNS-RAAS activity (ACEI, spirolactone etc.) a hyperkalaemic crisis may develop which threatens the patient with acidosis, dehydration, myoplegia, muscular spasms, however, in particular with fatal disorders of the cardiac rhythm. A similar effect may be exerted also by blockers of prostaglandin synthetase (non-steroid antirheumatics) and other drugs. The cause of IHH in diabetics is the coincidence of several pathogenic factors: 1. hypersecretion of ANF with hyperosmolar hyperglycaemic hypervolaemia and hyperfiltration already at the onset of DN, 2. early development of autonomous neuropathy of the sympathetic nerve, 3. reduced renin and prostaglandin formation already in the early stages of DN, 4. reduced extrarenal isorenin formation, 5. reduced conversion of prorenin into active renin, 6. reduced reactivity of the zona glomerulosa to AII, hyperkalaemia and ACTH for its functional reconstruction as a result of periodic activation of contraregulative hormones by fluctuations of the blood sugar level in diabetic patients, 7. reduced response of the distal renal tubule to aldosterone because of tubulointerstitial changes. IHH is thus another serious but rarely diagnosed late complication of diabetes which depends only partly on the stage of DN. It must be, however, diagnosed and respected with regard to the selection of drugs for the treatment of arterial hypertension and the syndrome of insulin resistance and the 5H syndrome resp., i.e. the association of hyperinsulinism which compensates insulin resistance with hyperglycaemia (NIDDM), hypertension, hyperlipoproteinaemia and hirsutism in women (so-called Stein-Leventhal syndrome).
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PMID:[Diabetic nephropathy and isolated hyporeninemic hypoaldosteronism]. 892 9

The syndrome of insulin resistance comprises the following H-phenomena: 1. Hyperinsulinism compensating the inborn postreceptor insulin resistance, 2. Hyperglycaemia-non-insulin-dependent diabetes mellitus, 3. Hyperlipoproteinaemia with android obesity, 4. Hypertension, 5. Hirsutism with the syndrome of polycystic ovaries as a manifestation of a hyperandrogenic situation in the female organism. Molecular syndromes of this syndrome of insulin resistance are obscure. They are the subject of intensive studies because H-phenomena are an aggregation of the main risk factors of atherogenesis. Recently attention is focused also on amylin--a 37 amino acid peptide with a 50% homologous amino acid sequence with a calcitonin-gene--related peptide (CGRP), which is the product of a gene made up of three introns on the 12th chromosome. Amylin acts in the beta-cells of the pancreas as a co-secretion of insulin. If in excess, it is deposited in the form of an amyloid in the beta-cells. In the early stage of NIDDM it alters the physiological response of the beta-cell to glycaemic stimuli and food, in later stages of the disease, after accumulation, it causes apoptosis of the beta-cell and reduces thus the secretory capacity of the Langerhans islets. It is excreted in the urine and thus, if the glomerular filtration is reduced, it cumulates in the blood stream and thus enhances insulin resistance already in the early stages of chronic renal insufficiency, or in diabetic nephropathy. In type II diabetes similarly as insulin levels also amylin levels are elevated, while in type I diabetes with early autoimmune destruction of the beta-cells the insulin and amylin levels are reduced or even zero. Amylin reduces in the muscle, probably by inhibition of glycogen synthase, the insulin stimulated non-oxidative utilization of glucose into muscle glycogen and conversely by stimulation of phosphorylase it stimulates glycogenolysis and thus also lactate production and gluconeogenesis in the liver which all are anti-insulin effects which intensify the insulin resistance of the main target tissues. Amylin, similarly as CGRP or calcitonin, reduces Ca blood levels and has a vasodilatating effect; it reduces the BP but in different minimal and maximal doses and by a different mechanism and via special receptors because the link of amylin to calcitonin receptors is 100 times lower and does not produce a rise of cAMP in the target cell. The effect on the enhancement of insulin resistance in muscle was proved also by direct measurements using an hyperinsulinaemic euglycaemic clamp. After prolongation of the clamp to more than two hours the effect on insulin resistance disappeared, although the hypocalcinaemic effect persisted. Amylin is able by its biological action to modify the secretion as well as the effectiveness of insulin to pathological values. These two characteristics are typical for impaired glucose tolerance in type II diabetes. Studies are under way to find out whether the effect of amylin is involved directly also in the pathogenesis of the other H-phenomena or only via accentuation of hyperinsulinism. In any case amylin is a new link the role of which in the pathogenesis of NIDDM and the syndrome of insulin resistance awaits evaluation. Due to its effect on gastric evacuation it participates also in the postprandial glycaemic control in particular in type I diabetes where it it begins to be used in therapy. Perhaps it will be possible to administer it in these patients along with insulin to improve diabetes compensation.
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PMID:[Amylin as an additional possible pathogenic factor in NIDDM and the insulin resistance syndrome]. 896 27

Recent evidence suggests that insulin is mitogenic on the adrenal cortex and stimulates adrenocortical tumor formation. We, investigated whether hyperinsulinemia is present in 13 patients with incidentally detected adrenal tumors. Patients with adrenal incidentalomas were obese (mean BMI 29.7 +/- 1.2 kg/m2, normal < 25; % body fat 35 +/- 1.5%, normal < 30%) with increased abdominal fat deposition (waist to hip ratio 0.92 +/- 0.02, normal < 0.85). All 13 patients were insulin resistant. Five had NIDDM, of the remaining patients 5 had fasting insulin concentrations above 15 microE/ml, and all 8 patients had elevated insulin concentrations after 75 g of glucose orally. To further investigate the potential role of insulin we examined its effects on the NCI-h295 cell line. Insulin (1-100 micrograms/ml) stimulated cell proliferation in a time and dose-dependent matter without affecting cortisol synthesis. At this concentrations insulin was equally potent to IGF I (10-80 ng/ml) or IGF II (10-100 ng/ml). We conclude that the majority of patients with adrenal incidentalomas are insulin-resistant/hyperinsulinemic. Insulin stimulates adrenal cancer cell lines in vitro. We propose that adrenal incidentalomas are a newly recognized manifestation of the metabolic syndrome comparable to insulin-mediated stimulation of the ovary in the polycystic ovary syndrome.
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PMID:Adrenal incidentalomas: a manifestation of the metabolic syndrome? 896 38

It is now clear that PCOS is often associated with profound insulin resistance as well as with defects in insulin secretion. These abnormalities, together with obesity, explain the substantially increased prevalence of glucose intolerance in PCOS. Moreover, since PCOS is an extremely common disorder, PCOS-related insulin resistance is an important cause of NIDDM in women (Table 3). The insulin resistance in at least 50% of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor. A factor extrinsic to the insulin receptor, presumably a serine/threonine kinase, causes this abnormality and is an example of an important new mechanism for human insulin resistance related to factors controlling insulin receptor signaling. Serine phosphorylation appears to modulate the activity of the key regulatory enzyme of androgen biosynthesis, P450c17. It is thus possible that a single defect produces both the insulin resistance and the hyperandrogenism in some PCOS women (Fig. 19). Recent studies strongly suggest that insulin is acting through its own receptor (rather than the IGF-I receptor) in PCOS to augment not only ovarian and adrenal steroidogenesis but also pituitary LH release. Indeed, the defect in insulin action appears to be selective, affecting glucose metabolism but not cell growth. Since PCOS usually has a menarchal age of onset, this makes it a particularly appropriate disorder in which to examine the ontogeny of defects in carbohydrate metabolism and for ascertaining large three-generation kindreds for positional cloning studies to identify NIDDM genes. Although the presence of lipid abnormalities, dysfibrinolysis, and insulin resistance would be predicted to place PCOS women at high risk for cardiovascular disease, appropriate prospective studies are necessary to directly assess this.
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PMID:Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. 940 43

Polycystic ovary syndrome (PCOS) is probably the most prevalent endocrinopathy in women and the most common cause of menstrual disturbances during the reproductive age. It is characterised by the presence of polycystic ovaries on ultrasound examination together with clinical and biochemical signs of hyperandrogenaemia. The majority of patients will seek medical advice because of menstrual disturbances, infertility or signs of hyperandrogeneamia (hirsutism, acne, alopecia). In obese patients the therapeutic mainstay is weight reduction. Anovulatory infertility is treated by stimulation of ovulation, laparoscopic electrocautery or IVF, while patients with menstrual disturbances without a wish to conceive should be treated with cyclic gestagen therapy or oral contraceptives in order to reduce the increased life-long risk of endometrial cancer. Additionally, hirsutism may be treated by epilation or antiandrogen therapy. PCOS is a common disease with an increased risk of NIDDM, hypertension, cardiovascular disease and endometrial cancer. Polycystic ovary syndrome is thus a disease which needs attention from the health system.
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PMID:[Polycystic ovary syndrome I. Clinical presentation and treatment]. 945 93

Polycystic ovary syndrome (PCOS) may be loosely defined as unexplained hyperandrogenism, with variable degrees of cutaneous symptoms, anovulatory symptoms, and obesity. The vast majority of patients with the full-blown Stein-Leventhal syndrome have functional ovarian hyperandrogenism (FOH). However, FOH often occurs without the LH excess or polycystic ovaries of classic PCOS. Functional adrenal hyperandrogenism (FAH) is often found in the syndrome, but it is less closely associated with anovulatory symptoms than is FOH. The vast majority of FOH seems to arise from abnormal regulation (dysregulation) of ovarian androgen secretion. This typically is due to escape from desensitization to luteinizing hormone (LH); this appears to occur because of a breakdown in the processes that normally coordinate ovarian androgen and oestrogen secretion so as to prevent hyperoestrogenism. Similar dysregulation of adrenal androgen secretion in response to ACTH seems to account for most FAH. Dysregulation of androgen secretion may affect the ovary alone (isolated FOH), the adrenal alone (isolated FAH), or both together. Modest insulin resistance is common in PCOS/FOH, and the resultant hyperinsulinaemia is a major candidate as the cause of the dysregulation. The hyperinsulinaemia may arise from either 'nature' (genetic defects) or 'nurture' (exogenous obesity). Although hyperinsulinaemia alone does not have an obvious effect on steroidogenesis, it may act in genetically predisposed women as a 'second hit' to unmask latent abnormalities in steroidogenesis. The ovary, the adrenal cortex, and several other organs paradoxically function as if responding to the hyperinsulinaemic state in spite of resistance to the effects of insulin on glucose metabolism. PCOS should be viewed as an early manifestation of a hyperinsulinaemic condition that will predispose to cardiovascular and metabolic complications later in life. A subset of PCOS patients appear to have not only insulin resistance but also beta-cell secretory dysfunction, which may indicate a relationship of the disorder to NIDDM. The fundamental genetic defects remain to be elucidated.
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PMID:Current concepts of polycystic ovary syndrome. 953 13

Up to 40% of women with polycystic ovary syndrome (PCOS) demonstrate some degree of glucose intolerance, either impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). Defects in insulin action have long-been recognized as characteristic in these women. Recently, evidence has been obtained which documents that insulin secretory dysfunction also contributes significantly to the observed glucose intolerance. This chapter will focus on the recent evidence supporting the specific roles of disordered insulin secretion and action, in the development of glucose intolerance in PCOS. In addition, the use of pharmacological agents that modify insulin action as therapeutic options for women with PCOS, will be discussed.
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PMID:Relation of functional ovarian hyperandrogenism to non-insulin dependent diabetes mellitus. 953 14

Androgenic disorders are those conditions in women characterized by excessive androgen action. They are the most common endocrinopathy of women, affecting from 10% to 20%. Signs are: persistent acne, hirsutism and androgenic alopecia, which is the female equivalent of male pattern baldness. A subgroup, those traditionally labeled as having polycystic ovary syndrome (PCOS), additionally have anovulation, as well as menstrual abnormalities and, often, obesity. Although women with androgenic disorders usually present themselves for help with the skin or menstrual changes, there are other important implications regarding their health. Women with PCOS have varying degrees of insulin resistance, and an increased incidence of Type II diabetes mellitus, as well as unfavorable lipid patterns. The presence of these risk factors is suggested by upper segment obesity, darkening of the skin, and the other skin changes that make up acanthosis nigricans. Diagnosis involves measurement of circulating androgens (of which free testosterone is most important), together with prolactin and FSH when menstrual dysfunction is present. Many women with androgenic skin changes have normal serum androgen levels, suggesting increased end organ sensitivity to androgens. Others have hyperandrogenism (of ovarian or adrenal origin). Treatment is usually successful in controlling acne, reducing hirsutism and stabilizing, or partially reversing, androgenic alopecia. Pharmacological approaches involve suppressing androgen levels, for example, the use of an appropriate oral contraceptive, or antagonizing androgen action with several medications that have this activity. Unfortunately, most women with androgenic disorders are frustrated in their efforts to obtain medical help. Understanding androgenic disorders will enable the physician to significantly help the majority of women with these conditions.
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PMID:Androgens and women's health. 960 8

According to the actual knowledge obesity is a serious, nutrition-dependent pathology with a high number of consequences. Endocrine sequence of obesity such as PCO-HAIR-syndrome (polycystic ovarian syndrome, hyperandrogenemia-insulin-resistance) with its cycle disorders and sterility are beginning already in adolescent and women of young reproductive age. With ageing more serious risks such as non-insulin dependent diabetes mellitus (NIDDM), arteriosclerosis followed by coronary disease, stroke and hypertension, metabolic syndrome and a higher prevalence of malignant diseases will appear. Based on these five risks obesity should be treated early when therapeutic strategies are more successful than in older ages. The definition of a diagnosis and the beginning of a weight reduction programme combined with intense motivating treatment as well as medical and psychotherapeutic guidance is an important preventive contribution.
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PMID:[Obesity--significance in adolescence and for reproduction]. 962 28

Polycystic ovary syndrome (PCOS) is a common disorder in premenopausal women and is characterized by hyperandrogenic chronic anovulation. The cause is unknown. PCOS is associated with significant insulin resistance as well as with defects in insulin secretion. These abnormalities place these women at substantial risk for developing type 2 diabetes mellitus. A defect in insulin-mediated receptor autophosphorylation has been found in a substantial proportion of PCOS women. Both PCOS and the insulin resistance that accompanies it appear to have major genetic components. Family studies of PCOS have supported this, although they suffer from incomplete phenotyping of probands and first-degree relatives. The phenotype in males and nonreproductive age females is uncertain. Despite the shortcomings of the family studies of PCOS, they have consistently indicated familial clustering and suggested that the mode of inheritance is dominant. Our initial studies of 50 families of PCOS probands indicate that 24% of sisters are affected with PCOS. There also appears to be an intermediate phenotype of sisters with regular menstrual cycles who are hyperandrogenic per se (22% of sisters). Additionally, there appears to be a major familial defect, with 50% of first-degree relatives having glucose intolerance (impaired glucose tolerance by oral glucose tolerance test or type 2 diabetes mellitus). These findings suggest that hyperandrogenism in females and glucose intolerance may be genetic traits in PCOS kindreds. Systematic phenotyping will allow assignment of affected status for eventual linkage analysis.
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PMID:Phenotype and genotype in polycystic ovary syndrome. 976 10


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