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 syndromes of extreme severe insulin resistance are mainly caused by genetic defects of the insulin receptor gene (Type A syndrome, Leprechaunism, and Rabson-Mendenhall syndrome) or by the presence of circulating autoantibodies that disrupt the normal functions of the insulin receptor (Type B syndrome). These syndromes are characterized by the hyperinsulinemia and severe insulin resistance and in most cases accompanied by impaired glucose tolerance and diabetes mellitus. The clinical features common to these syndromes are acanthosis nigricans, hyperandrogenism and ovarian dysfunction. On the other hand, an important distinguishing typical feature in type B syndrome is evidence of other autoimmune disorders. [These syndromes can be a contributory causes of insulin resistance in a subpopulation with NIDDM.]
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PMID:[Syndromes of severe insulin resistance]. 1019 43

Polycystic ovary syndrome (PCOS) is classically characterised by ovarian dysfunction (oligomenorrhoea, anovulation and infertility), androgen excess (hirsutism and acne), obesity, and morphological abnormalities of the ovaries (cystic enlargement and stromal expansion). More recently, insulin resistance has been found to be common in PCOS, along with an increased prevalence of other features of the "metabolic syndrome", namely glucose intolerance, type 2 diabetes mellitus, and hyperlipidaemia. Hyperinsulinaemia is likely to contribute to the disordered ovarian function and androgen excess of PCOS. Reducing insulin resistance by lifestyle modifications such as diet and exercise improves endocrine and menstrual function in PCOS. These lifestyle modifications are the best initial means of improving insulin resistance. Metformin, an oral hypoglycaemic agent that increases insulin sensitivity, has been shown to reduce serum concentrations of insulin and androgens, to reduce hirsutism, and to improve ovulation rates. The effect of metformin alone on fertility rates is unknown. Some studies suggest that metformin will reduce total body weight to a small extent, but with a predominant effect on visceral adipose reduction. The effects of metformin on lipid abnormalities, hypertension or premature vascular disease are unknown, but the relative safety, moderate cost, and efficacy in reducing insulin resistance suggest that metformin may prove to be of benefit in combating these components of the "metabolic" syndrome in PCOS. Further properly planned randomised controlled trials are required.
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PMID:Metformin and intervention in polycystic ovary syndrome. Endocrine Society of Australia, the Australian Diabetes Society and the Australian Paediatric Endocrine Group. 1145 23

Since the 1990 NIH-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome and, as such, no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include: menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
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PMID:Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). 1468 54

Since the 1990 National Institutes of Health-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome, and as such no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
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PMID:Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. 1471 38

The current consensus on diagnostic criteria of polycystic ovary syndrome has concluded that it is a syndrome of ovarian dysfunction along with hyperandrogenism and morphology of polycystic ovary. The clinical manifestations may include irregular menses, androgen excess, and obesity, but insulin resistance is also a common feature. There is an increased risk of type 2 diabetes mellitus. Treatment of polycystic ovary includes ovulation induction, amelioration of androgen signs and correction of insulin resistance.
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PMID:[Current criterion for diagnosing polycystic ovary syndrome]. 1546 47

The insulin resistance syndrome, also referred to as the metabolic syndrome or syndrome X, is associated with a primary cellular defect in insulin action (insulin resistance) and a compensatory increase in insulin secretion. The combination of insulin resistance and subsequent hyperinsulinaemia causes a number of metabolic and cardiovascular changes that result in a syndrome typically characterised by type 2 diabetes, obesity, dyslipidaemia, coronary artery disease and hypertension. Moreover, disturbances in sleep (sleep apnoea) and ovarian dysfunction are also characterised by insulin resistance. The pathophysiological basis for these disturbances reflects the impact of variable genetic and environmental influences. At a molecular level, insulin resistance involves defects of insulin signalling such as reduced insulin receptor tyrosine kinase activity and reduced post-receptor phosphorylation steps that impinge on metabolic and vascular effects of insulin.
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PMID:The insulin resistance syndrome: physiological considerations. 1746 39

Polycystic ovary syndrome (PCOS) is a major risk factor for impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2D). Several studies have examined possible mechanisms related to glucose metabolism and insulin secretion that may be responsible for the high prevalence of disorders of glucose metabolism in women with PCOS. The actual pathogenic mechanisms appear to be complex and multifactorial, possibly characterized by the lack of uniformity between patients, thus reflecting the heterogeneity of PCOS. Impaired insulin action and/or beta-cell dysfunction and/or decreased hepatic clearance of insulin have been implicated so far. This article focuses on the role of beta-cell function in the increased predisposition to GDM and T2D in PCOS and the possible genetic basis of defects in insulin secretion. Conditions, like pregnancy and exogenous glucocorticoid administration, aggravate insulin resistance ,thereby placing additional strains upon beta-cells, which may be inherently prone to dysfunction in women with PCOS. The aggravation of insulin resistance amplifies the demands for insulin secretion by beta-cells. The resultant unfavourable state unmasks potential latent defects of beta-cell function, thereby possibly precipitating the development of T2D or of gestational diabetes (GDM) in pregnant women with PCOS. In addition to metabolic sequelae, insulin resistance and compensatory hyperinsulinemia contribute to ovarian dysfunction,manifested by hyperandrogenemia and anovulation, characterizing PCOS. The role of ovarian androgen excess in metabolic aberrations,specifically insulin action and secretion remains unclears.
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PMID:Pancreatic beta-cells dysfunction in polycystic ovary syndrome. 1907 72

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. It affects 6% to 7% of the population and is characterized by hyperandrogenism and ovarian dysfunction. Women with the disorder often present with insulin resistance and obesity, making it importance for health care providers to monitor closely for signs and symptoms of metabolic syndrome and type 2 diabetes. Treatments are targeted toward improving insulin tolerance, reducing signs and symptoms of hyperandrogenism (hirsutism, anovulation, etc), restoring normal menstrual cycle function, and restoring fertility. Major treatment should include weight management through diet and exercise, regardless of body mass index and might include concurrent drug therapy. It is important that pharmacists understand the underlying pathophysiology of the disease and the available treatments, in addition to the importance of reducing risk of metabolic syndrome/type 2 diabetes, and cardiovascular disease in these patients.
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PMID:Polycystic ovary syndrome: an overview. 2165 66

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age and is associated with various metabolic perturbations, in addition to chronic anovulation and factors related to androgen excess. In general, women live longer than men and develop cardiovascular disease at an older age. However, women with PCOS, as compared with age- and body mass index-matched women without the syndrome, appear to have a higher risk of insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and an increased prothrombotic state, possibly resulting in a higher rate of type 2 diabetes mellitus, fatty liver disease, subclinical atherosclerosis, vascular dysfunction, and finally cardiovascular disease and mortality. Further alterations in PCOS include an increased prevalence of sleep apnea, as well as various changes in the secretion and/or function of adipokines, adipose tissue-derived proinflammatory factors and gut hormones, all of them with direct or indirect influences on the complex signaling network that regulates metabolism, insulin sensitivity, and energy homeostasis. Reviews on the cardiometabolic aspects of PCOS are rare, and our knowledge from recent studies is expanding rapidly. Therefore, it is the aim of the present review to discuss and to summarize the current knowledge, focusing on the alterations of cardiometabolic factors in women with PCOS. Further insight into this network of factors may facilitate finding therapeutic targets that should ameliorate not only ovarian dysfunction but also the various cardiometabolic alterations related to the syndrome.
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PMID:Cardiometabolic aspects of the polycystic ovary syndrome. 2282 62

A pathophysiology paradigm shift has emerged with the discovery that polycystic ovary syndrome (PCOS) is a proinflammatory state. Despite the dogma that the compensatory hyperinsulinemia of insulin resistance is the promoter of hyperandrogenism, physiological insulin infusion has no effect on androgen levels in PCOS. The dogma also does not explain the cause of hyperandrogenism and ovarian dysfunction in the 30 to 50% of women with PCOS who are of normal weight and lack insulin resistance. Inflammation is the underpinning of insulin resistance in obesity and type 2 diabetes, and may also be the cause of insulin resistance when present in PCOS. The origin of inflammation in PCOS has been ascribed to excess abdominal adiposity or frank obesity. However, nutrients such as glucose and saturated fat can incite inflammation from circulating mononuclear cells (MNC) of women with PCOS independent of excess adiposity and insulin resistance, and can also promote atherogenesis. Hyperandrogenism activates MNC in the fasting state to increase MNC sensitivity to nutrients, and is a potential mechanism for initiating inflammation in PCOS. However, chronic ovarian androgen suppression does not reduce inflammation in normal-weight women with PCOS. Direct exposure of ovarian theca cells to proinflammatory stimuli in vitro increases androgen production. These findings may be corroborated in vivo with anti-inflammatory therapy to normal-weight insulin-sensitive women with PCOS without abdominal adiposity to observe for amelioration of ovarian dysfunction.
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PMID:Nutrient-Induced Inflammation in Polycystic Ovary Syndrome: Role in the Development of Metabolic Aberration and Ovarian Dysfunction. 2613 32


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