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)

Polycystic ovary syndrome (PCOS) is a heterogeneous familial disorder characterized by chronic anovulation and hyperandrogenism. This multi-system, polygenic, multi-factorial disorder is associated with an increased risk for metabolic abnormalities such as type 2 diabetes mellitus. Signs and symptoms of PCOS often emerge during the peri-pubertal years with premature pubarche (PP) being the earliest manifestation for some girls. Insulin resistance and hyperinsulinemia are important pathophysiological features that are common to both PP and PCOS. Future investigations are needed to uncover the relevant genetic and hormonal factors and identify effective interventions.
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PMID:Puberty and polycystic ovary syndrome. 1675 May 96

Polycystic ovary syndrome (PCOS) is increasingly being recognized in adolescent girls seeking treatment for signs and symptoms of hyperandrogenism. It is difficult to diagnose PCOS in adolescents, therefore a high index of suspicion is necessary. Timely screening and treatment are crucial because another important component of the syndrome is insulin resistance/hyperinsulinemia increasing the risk for type 2 diabetes, dyslipidemia, and cardiovascular sequelae. Diagnosis of PCOS in adolescents should include a thorough family history, exclusion of other causes of hyperandrogenism, and appropriate laboratory evaluation. The scarcity of controlled clinical trials makes treatment controversial. Therapeutic options include lifestyle intervention, oral contraceptive pills, and insulin sensitizers. Long-term follow-up is needed to determine the effectiveness of these approaches in changing the natural history of the reproductive and metabolic outcomes without causing undue harm.
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PMID:Treatment of PCOS in adolescence. 1677 60

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (>/=65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21-0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS.
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PMID:Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study. 1696 11

Polycystic ovary syndrome (PCOS), the main androgen disorder in women. Recently, it has been suggested that the condition is hereditary and that women with PCOS have disturbances, such as hyperandrogenism and additional metabolic abnormalities as hyperinsulinaemia, increased insulin resistance, dyslipidemia. Polycystic ovary syndrome (PCOS) usually arises during puberty and is marked by hyperinsulinemia and hyperandrogenism. Adolescents with PCOS are at an increased risk of developing health problems later on in life such as type 2 diabetes, cardiovascular disease, and infertility. Furthermore, the physical signs of PCOS can be detrimental to a teenage girl's self-image. Early diagnosis and treatment of PCOS in adolescents are essential in ensuring adulthood health and restoring self-esteem. Treatment for an adolescent with PCOS includes diet and exercise, metformin, and oral contraceptive pills. Still, surgery is not indicated in teenagers. Furthermore, psychological factors must be taken into consideration as well.
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PMID:[Early metabolic abnormalities--insulin resistance, hyperinsulinemia, impaired glucose tolerance and diabetes, in adolescent girls with polycystic ovarian syndrome]. 1708 Jul 48

Thiazolidinediones (TZDs) such as pioglitazone and rosiglitazone are widely used as insulin sensitizers in the treatment of type 2 diabetes. In diabetic women with polycystic ovary syndrome, treatment with pioglitazone or rosiglitazone improves insulin resistance and hyperandrogenism, but the mechanism by which TZDs down-regulate androgen production is unknown. Androgens are synthesized in the human gonads as well as the adrenals. We studied the regulation of androgen production by analyzing the effect of pioglitazone and rosiglitazone on steroidogenesis in human adrenal NCI-H295R cells, an established in vitro model of steroidogenesis of the human adrenal cortex. Both TZDs changed the steroid profile of the NCI-H295R cells and inhibited the activities of P450c17 and 3betaHSDII, key enzymes of androgen biosynthesis. Pioglitazone but not rosiglitazone inhibited the expression of the CYP17 and HSD3B2 genes. Likewise, pioglitazone repressed basal and 8-bromo-cAMP-stimulated activities of CYP17 and HSD3B2 promoter reporters in NCI-H295R cells. However, pioglitazone did not change the activity of a cAMP-responsive luciferase reporter, indicating that it does not influence cAMP/protein kinase A/cAMP response element-binding protein pathway signaling. Although peroxisome proliferator-activated receptor gamma (PPARgamma) is the nuclear receptor for TZDs, suppression of PPARgamma by small interfering RNA technique did not alter the inhibitory effect of pioglitazone on CYP17 and HSD3B2 expression, suggesting that the action of pioglitazone is independent of PPARgamma. On the other hand, treatment of NCI-H295R cells with mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) enhanced promoter activity and expression of CYP17. This effect was reversed by pioglitazone treatment, indicating that the MEK/ERK signaling pathway plays a role in regulating androgen biosynthesis by pioglitazone.
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PMID:Pioglitazone inhibits androgen production in NCI-H295R cells by regulating gene expression of CYP17 and HSD3B2. 1713 41

Polycystic ovary syndrome affects 6%-7% of reproductive-aged women, making it the most common endocrine disorder in this population. It is characterized by chronic anovulation and hyperandrogenism. Affected women may present with reproductive manifestations such as irregular menses or infertility, or cutaneous manifestations, including hirsutism, acne, or male-pattern hair loss. Over the past decade, several serious metabolic complications also have been associated with polycystic ovary syndrome including type 2 diabetes mellitus, metabolic syndrome, sleep apnea, and possibly cardiovascular disease and nonalcoholic fatty liver disease. In addition to treating symptoms by regulating menstrual cycles and improving hyperandrogenism, it is imperative that clinicians recognize and treat metabolic complications. Lifestyle therapies are first-line treatment in women with polycystic ovary syndrome, particularly if they are overweight. Pharmacological therapies are also available and should be tailored on an individual basis. This article reviews the diagnosis, clinical manifestations, metabolic complications, and treatment of the syndrome. A table summarizing treatment recommendations is provided.
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PMID:Polycystic ovary syndrome: diagnosis and treatment. 1727 49

Polycystic ovary syndrome (PCOS), one of the most common causes of ovulatory infertility, affects 4-7% of women. Although it was considered that PCOS may have some genetic component and that clinical features of this disorder may change throughout a life span, starting from adolescence to postmenopausal age, no effort has been made to define differences in the phenotype and clinical presentation according to age. Indeed, it has been widely recognized in the last decade that several features of metabolic syndrome (MS), particularly insulin resistance and hyperinsulinemia, are inconsistently present in the majority of women with PCOS. This represents an important factor in the evaluation of PCOS throughout life, which implies that PCOS by itself may not be a hyperandrogenic disorder exclusively related to young and fertile-aged women, but may also have some health implications later in life. In young women with PCOS, hyperandrogenism, menses irregularities, and insulin resistance may occur together, emphasizing the pathophysiological role of excess androgen and insulin on PCOS. Hyperandrogenism and infertility represent the major complaints of PCOS in adult fertile age. In addition, obesity and MS may affect more than half these women. Later in life, it becomes clear that the association of obesity (particularly the abdominal phenotype) and PCOS renders affected women more susceptible to develop type 2 diabetes mellitus (T2DM), with some difference in the prevalence rates among countries, suggesting that environmental factors are important in determining individual susceptibility. Little is known about ovarian morphology and androgen production in women with PCOS after menopause. Some studies found that morphological ultrasonographic features consistent with polycystic ovaries are very common in postmenopausal women, and that these features are associated with higher than normal testosterone levels and metabolic alterations. There is an obvious need for further research in this area. Identification of major complaints and features of PCOS during the different ages of an affected woman may help, in fact, to plan individual therapeutic strategies, and, possibly, prevent long-term chronic metabolic diseases.
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PMID:Polycystic ovary syndrome: a multifaceted disease from adolescence to adult age. 1730 42

Epilepsy in women is relatively often linked with reproductive disorders which include polycystic ovarian syndrome, hypothalamic amenorrhea and functional hyperprolactinaemia. These disorders have a significant share in a high incidence of infertility and premature menopause while the polycystic ovarian syndrome, also manifested by the metabolic syndrome, places the affected patients at risk of later consequences such as type 2 diabetes mellitus, cardiovascular diseases including arterial hypertension, gynaecological neoplasias (the breast and the endometrium), and in the case of pregnancy, a higher incidence of pregnancy induced hypertension. Apart from epilepsy as such, also antiepileptic treatment may have negative impact on the female's reproductive functions. In many cases, adverse effects of treatment complicate the patient's life more than the attacks alone. Medication induced weight gain might be responsible for different endocrine diseases (menstruation disorders, polycystic ovarian syndrome, hyperandrogenism). The article analyses the influence of side effects of the different antiepileptic drugs on the development of metabolic and endocrine anomalies. The role of antiepileptic drugs in the development of reproductive and endocrine disorders was first described by Isojarvim in 1993. A high incidence of polycystic ovarian syndrome and/or hyperandrogenism (43%) was observed in women taking valproat, which was clearly higher than in women taking other antiepileptics. Results reported in literature are rather controversial. The article gives an overview of current knowledge with respect to the influence of epilepsy and antiepileptics on the incidence ofpolycystic ovarian syndrome, which is considerably higher in women with epilepsy (10-25%) than in the unaffected population (4-7%), and of the related metabolic syndrome. The article concludes with recommendations for clinical practice in the treatment of epilepsy in women in reproductive age.
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PMID:[Epilepsy and disorders of reproduction]. 1747 15

Insulin resistance (IR) in childhood has importance to the understanding and prevention of the growing epidemic of insulin resistance syndrome (IRS) in adults with attendant obesity, type 2 diabetes (T2DM), atherosclerotic diseases, hypertension, gout, non-alcoholic, steato-hepatitis (NASH), gall bladder disease, nephropathy, polycystic ovarian disease (PCOS), infertility and premature senility. The severity of IR and its' complications in children unfortunately and usually progresses in their pubertal transition to adulthood; affected young children are more likely than adults to have underlying causal monogenic disorders; the sequence of natural history and events give insights into disease pathogeneses, and optimal life style choices that last are best made during the early formative years. Some features of IR in children discussed herein are: a strong tendency to low birth weight for gestational age, adverse effects of adrenarche and therapeutic steroid therapy, predisposition to premature pubarche, acanthosis nigricans, tall stature despite pituitary GH suppression, allergic diathesis, hyperandrogenism and PCOS, dyslipidemia and fatty liver disease, and diagnosis by clinical and biochemical markers of IR including insulin regulated hepatic hormonal binding proteins such as IGFBP-1. The national preoccupation with the "metabolic syndrome" T2DM and obesity, should be appropriately directed to an improved understanding of IR in children and their management, if the looming health crisis in affected adults is to be seriously addressed. The nation is facing its' first generation of children who will be less healthy and die younger than the previous generation (Marks (2005) Presentation to the American Association of Diabetes Educators 32nd Annual Meeting and Exhibition, August 10-13, Washington, DC).
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PMID:Childhood obesity and insulin resistance. 1770 76

Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects about one in 15 women worldwide. The major endocrine disruption is excessive androgen secretion or activity, and a large proportion of women also have abnormal insulin activity. Many body systems are affected in polycystic ovary syndrome, resulting in several health complications, including menstrual dysfunction, infertility, hirsutism, acne, obesity, and metabolic syndrome. Women with this disorder have an established increased risk of developing type 2 diabetes and a still debated increased risk of cardiovascular disease. The diagnostic traits of polycystic ovary syndrome are hyperandrogenism, chronic anovulation, and polycystic ovaries, after exclusion of other conditions that cause these same features. A conclusive definition of the disorder and the importance of the three diagnostic criteria relative to each other remain controversial. The cause of polycystic ovary syndrome is unknown, but studies suggest a strong genetic component that is affected by gestational environment, lifestyle factors, or both.
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PMID:Polycystic ovary syndrome. 1772 20


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