Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrophobic attractive force is the major force in maintaining the stability of biomembranes, yielding coordinated functionality to the embedded proteins that they contain. This force between the composite linear hydrocarbons of the biomembranes is a function of their length and their mutual parallel distance from each other, and is extremely sensitive to this distance. Extracellular, natural linear hydrocarbons of certain length and shape can intercalate into lipid matrix of the biomembranes, reducing their innate hydrophobic net strength in a concentration-dependent manner, making them loose, leaky, and thus gaining the credence of stimulus-generating agents. In physiological circulatory concentration, these molecules may have a role for the maintenance of cellular homeostasis. However, in stagnating physiological excess, these same agents can become acutely or chronically stimulating and, therefore, disease-precipitating. Such situations do exist in the clinical disorders of acne, atherosclerosis, acute pancreatitis, diabetes, diabetic retinopathy, homocysteinemea, and stress. A systematic approach, beginning with surface film studies with the suspect linear hydrocarbons, can be followed up with in vitro and in vivo studies. This should substantiate or negate the view presented here. Isolated information, along these lines, already exist in literature. The example of acne is a suitable starting point to elaborate this view, for sebaceous gland of the human pilosebaceous unit (PSU) contains all the exemplary, stimulus-inducing linear hydrocarbons to generate surface-reaction on the pilosebaceous ductal surface.
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PMID:Disruption of hydrophobic stability of biomembranes is the earliest event in several clinical disorders. 1528 77

The aim of this study was to investigate the phenotypic parameters and associated factors characterizing the development of glucose intolerance in polycystic ovary syndrome (PCOS). Among the 121 PCOS female subjects from the Mediterranean region, 15.7 and 2.5% displayed impaired glucose tolerance and type 2 diabetes, respectively. These subjects were included in a single group of overweight or obese subjects presenting with glucose intolerance (GI) states. PCOS women with normal glucose tolerance (81.8%) were subdivided into two groups: those who were overweight or obese and those of normal weight. Metabolic and hormonal characteristics of the GI group included significantly higher fasting and glucose-stimulated insulin levels, more severe insulin resistance, hyperandrogenemia, and significantly higher cortisol and androstenedione responses to 1-24 ACTH stimulation. One important finding was that lower birth weight and earlier age of menarche were associated with GI in PCOS women. Frequency of hirsutism, oligomenorrhea, acne, and acanthosis nigricans did not characterize women with GI. Our findings indicate that PCOS patients with GI represent a subgroup with specific clinical and hormonal characteristics. Our observations may have an important impact in preventative and therapeutic strategies.
Diabetes 2004 Sep
PMID:Glucose intolerance in a large cohort of mediterranean women with polycystic ovary syndrome: phenotype and associated factors. 1533 45

Polycystic ovary syndrome (PCOS) has traditionally been thought of as a triad of oligomenorrhea, hirsutism, and obesity. PCOS is now recognized as a heterogeneous disorder that results in overproduction of androgens primarily from the ovary leading to anovulation and hirsutism and is associated with insulin resistance. Symptoms in the adolescent include oligomenorrhea, hirsutism, acne, and weight gain. These symptoms are often attributed to normal pubertal events, which can lead to a delay in diagnosis. Insulin resistance, impaired glucose tolerance and diabetes have been shown to occur in adolescents with PCOS. Treatment should be instituted early to decrease symptoms and long-term sequellae of PCOS. Weight loss, oral contraceptives and antiandrogens are very effective in treating the symptoms of this disorder. Insulin-sensitizing medications show promise, but should be used with caution until larger randomized trials have shown short- and long-term benefit and efficacy over traditional therapies in the adolescent population.
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PMID:Polycystic ovary syndrome in adolescent girls. 1584 68

Atypical endometrial hyperplasia has been associated with progression to endometrial cancer, the most common genital malignancy. There are multiple risk factors for endometrial cancer, such as early menarche, exogenous estrogen exposure, obesity and diabetes. Diabetics have a 3-4 fold relative risk of endometrial cancer. Also, several studies have demonstrated an association between insulin resistance and endometrial cancer. There is known the first description of atypical endometrial hyperplasia resistant to progestogen therapy, which was subsequently treated with an insulin-sensitizng agent, metformin. Metformin is a biguanide antihyperglycemic agent used in the treatment of adult-onset diabetes. Unlike the sulfonylureas, metformin does not act primarily by increasing insulin secretion. In contrast, metformin lowers the rate of gluconeogenesis in the presence of insulin. Therefore, it is considered an insulin-sensitizer. Increased insulin sensitivity may improve the metabolic effect of insulin and decrease its mitogenic effect by tissue-specific mechanisms. One explanation for tissue specific differences in insulin binding and action may be through the relative expression of the insulin receptor (IR) isoforms. The IR isoforms IR-A and IR-D differ by 12 amino acid residues, owing to the alternative splicing of exon. The IR-A is predominantly expressed in malignant tissues and may lead to mitogenic effects within the cell. The relative expressions of IR-A and IR-B in normal and malignant endometrial tissue is not known. Besides direct effects on the IR, several additional mechanisms have been proposed for the mitogenic effect of insulin in endometrial cancer. In addition to the possible direct mitogenic effects of insulin through the IR-A, insulin resistance may be associated with alterations in expression of insulin-like growth factors (IGFs) and the IGF binding proteins (IGFBPs) or may inhibit the protective effect of progestagens. Binding sites for IGF-1 and IGF-2 have been confirmed in both normal and malignant endometrium. Binding of IGF-1 is significantly higher in endometrial cancer compared to normal endometrium. In the Ishikawa human endometrial cancer cell line IGF-1 was a more potent mitogen than insulin or IGF-2. Insulin may increase mitogenicity by regulating the expression of IGFBPs. The IGFBPs are a family of proteins that have both proliferative and anti-proliferative effects. While all six high-affinity IGFBPs are expressed in the endometrium, IGFBP-1 is the best characterized. Hyperinsulinemia can decrease IGFBP-1 even in the presence of progesterone, perhaps inhibiting progesterone's protective effects. Interestingly, IGFBP-1 was undetectable or minimally expressed in endometrial cancers. Nestler discussed results of a 6-month treatment of 100 nonebese women with PCOS, which showed a somewhat greater effect of metformin than rosiglitazone and no benefit of administering both agents in combination. Long-term treatment with oral contraceptives decreases endometrial cancer, with a reduction in serum androgens and a decreases in hirsutism and acne, but may worsen insulin resistance and lead to deteriration in glucose tolerance. Insulin sensitizers, on the other hand, should decrease endometrial hyperplasia by inducing regular menses, but may not be as beneficial in improving androgen - related symptoms. Note that the Nurses Health Study (NHS) showed increased risk of diabetes in oral contraceptive users. These considerations may be related to the finding that women who used oral contraceptives have increased risk of myocardial infarction. Thus, in view of the particular increase in CVD risk among women with PCOS, one might be less likely to recommend oral contraceptives, while insulin sensitizers may be of particular benefit, decreasing androgens, improving ovulation and fertility, and reducing the risk of diabetes and CVD. Theoretically, metformin, a treatment which is now widely used to treat infertile women with PCOS, may have a role in preventing endometrial hyperstimulation by lowering insulin concentrations and restoring ovulation. However, the long-term effects of this drug in women with PCOS are not known and more studies are required before suggesting its use for preventing endometrial cancer.
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PMID:[Molecular action of insulin-sensitizing agents]. 1635 Jul 24

Polycystic ovary syndrome (PCOS) is a diagnosis made between late adolescence and the menopause in 5-10% of women. PCOS is a heterogeneous disorder of unknown etiology characterized by hyperandrogenic chronic anovulation. This syndrome consists of a diverse constellation of signs and symptoms, such as hirsutism, acne, acanthosis nigricans, obesity, menstrual irregularities, anovulation, and/or infertility. Features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia, are common in this patient population. Recent insights into the pathophysiology of PCOS have shown insulin resistance and hyperinsulinemia to play a substantial role. Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Recent studies show that serum levels of inflammatory mediators, such as tumor necrosis factor-alpha and interleukin-6, are increased in the insulin-resistant conditions of obesity and PCOS. The optimal modality for long-term treatment should have positive effects on androgen synthesis, sex hormone-binding globulin production, the lipid profile, insulin sensitivity, inflammatory mediators, and clinical symptoms including acne, hirsutism, and irregular menstrual cycles. Treatment with insulin-sensitizing agents is a relatively new therapeutic strategy in women with PCOS. Current research has shown that the use of diabetes mellitus management practices aimed at reducing insulin resistance and hyperinsulinemia (such as weight reduction and the administration of oral antidiabetic drugs) can not only reverse testosterone and luteinizing hormone abnormalities and restore menstrual cycles, but can also improve glucose, insulin, proinflammatory cytokine, and lipid profiles.Clinical treatment with troglitazone, a member of the thiazolidinedione family, for the management of PCOS complications such as insulin resistance, hyperandrogenism, and anovulation was found to have beneficial effects; however, it was taken off the market over concerns of hepatotoxicity. Although troglitazone is no longer available in the US, numerous clinical trials have established the role of thiazolidinediones in the treatment of women with PCOS. Clinical data emerging regarding the utility of two of the newer, safer thiazolidinediones, pioglitazone and rosiglitazone, for this patient population, consistently demonstrate effective improvements of endocrine and ovulatory performance in women with PCOS. The benefit and importance of lifestyle modification and weight reduction, when it can be achieved, is still an important component in the long-term treatment of PCOS. Pharmacologic reduction in insulin levels using thiazolidinediones appears to offer another therapeutic modality for PCOS, which may ameliorate the progress of both hyperinsulinemia and hyperandrogenism. However, additional studies of patients so treated are necessary before these agents can be considered first-line treatment for PCOS. Convincing data from randomized controlled trials with sufficient power to detect both the benefits and risks of long-term treatment with thiazolidinediones in women with PCOS remain to be obtained.
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PMID:Thiazolidinediones for the therapeutic management of polycystic ovary syndrome : impact on metabolic and reproductive abnormalities. 1667 59

The prevalence and relevance of polycystic ovaries (PCO) in German women with polycystic ovary syndrome has not been evaluated. This retrospective study included 212 PCOS patients (mean age 28 years) diagnosed by the NIH-criteria and consecutively recruited since 2003. Clinical features including anthropometric variables and the degree of hirsutism, family history, menstrual cyclicity as well as endocrine biochemical parameters were recorded. In addition, 3-h oral glucose tolerance testing for indices of insulin resistance and glucose metabolism was performed in each patient. Transvaginal ultrasound was used to detect polcystic ovaries, defined as the presence of at least one ovary > 10 ml or with at least 12 follicles of 2-9 mm diameter. In this German PCOS cohort, PCO were identified in 166 women (78%). Women with PCO (PXO+) had significantly higher LH/FSH ratios (median 2.1 vs. 1.7) and IGF-1 levels (median 182.5 vs. 160.5 ng/ml) compared to patients without PCO (PCO-). In addition, a significantly higher prevalence of acne (50% vs. 33%) and higher hirsutism scores (median 9 vs. 7) were found in PCO+ patients. Testosterone levels and the free androgen index (FAI) correlated significantly with ovarian volume and the number of ovarian follicles. Also, a subgroup of PCO+ women with a combination of increased ovarian volume and follicle number had higher testosterone levels (median 3.1 vs. 2.1 nmol/l) and FAI (median 7.6 vs. 4.5) compared to women with increased follicle count but normal volume. No differences were found in metabolic parameters or insulin resistance indices. PCO are common finding in German PCOS women. PCO appear to be associated with a more pronounced hyperandrogenemia, especially when both ovarian volume and follicle number are increased.
Exp Clin Endocrinol Diabetes 2006 Apr
PMID:The combination of increased ovarian volume and follicle number is associated with more severe hyperandrogenism in German women with polycystic ovary syndrome. 1670 49

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in United States, affecting 6-10% of females in the reproductive age group. Recent studies have shown that insulin resistance plays an important role in the pathogenesis of PCOS. Traditionally, management of PCOS consisted mainly of ovulation induction, treatment of acne and hirsutism, and prevention of endometrial cancer. However, with mounting evidence showing that PCOS is associated with dysmetabolic syndrome and an increased risk for developing diabetes and heart disease, this can no longer be our sole focus. Current data support a strong recommendation that women with PCOS should undergo comprehensive evaluation for diabetes and recognized cardiovascular risk factors and receive appropriate treatment as needed. Lifestyle modifications remain the first-line therapy for all obese women with PCOS. However, many obese women with PCOS find weight loss difficult to achieve and maintain, and this is not an option for lean women with PCOS. For these reasons, insulin-sensitizing drugs are proving to be a promising and unique therapeutic option for chronic treatment of PCOS.
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PMID:Prevention of diabetes and cardiovascular disease in women with PCOS: treatment with insulin sensitizers. 1677 55

This study was undertaken to document prevalence, motives and observed complications of steroid use as a depigmenting agent amongst African blacks in southeast Nigeria. This practice is very common in the African environment. Consecutive new patients attending the dermatology clinic of the University of Nigeria TeachingHospital, Enugu, from June to December 2004 were recruited. Active substances of products used were determined from packages, while unknown concoctions were analyzed. Chi-squared and Fischer tests were used for statistical analysis, with a significant threshold fixed at 5%. Females aged 18-69 years accounted for 75% (414) of patients. Main topical steroids used by both women and men were class-1 steroids, and these were often compounded with other bleaching products. Median duration of usage was 9 years +/- 1.3. Disorders observed included steroid-induced acne (45.3%), macular hyperpigmentation of face (37.2%), mycoses (40.4%), striae (28.3%), telangiectasis (21.3%), hypertrichosis (13.9%) and diabetes mellitus (2.1%). Duration of utilization of these topical steroids was significantly associated with severe local and systemic consequences, while withdrawal of the offending steroids usually resulted in severe withdrawal dermatitis that was unpleasant to patients. This may suggest that discontinuation is impossible.
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PMID:Topical steroid abuse: its use as a depigmenting agent. 1677 16

Polycystic ovary syndrome (PCOS) is a very common disorder affecting 5-10% of women of reproductive age. The pivotal endocrine abnormalities of this syndrome are insulin resistance and ovarian and, to a lesser degree, adrenal hypersensitivity to hormonal stimulation. PCOS may manifest itself as early as the first decade of life by premature pubarche or menarche. Oligoamenorrhea in the first postpubarchal years, although very common, may be an early symptom of PCOS, especially in overweight girls with hirsutism or acne. Girls with low birth weight as well as a family history of diabetes mellitus or premature cardiovascular disease are at high risk for developing PCOS. Circulating bioavailable testosterone levels are usually elevated, while total testosterone may be normal due to low levels of sex hormone-binding globulin. The typical sonographic appearance of PCOS ovaries consists of high ovarian volume (>10 mL) and the presence of 12 or more follicles in each ovary measuring 2-9 mm in diameter. However, this finding is not specific, since it may occur in >20% of healthy girls. The therapeutic goals in adolescents with PCOS is first to restore bodyweight and menses and to reduce the signs of hyperandrogenism. The reduction of bodyweight in this young age group may require the collaboration of the pediatrician, dietitian, and psychotherapist. The adolescent should be urged to adopt a healthy lifestyle with the aim to maintain a normal body mass index throughout adolescence and adult life. The choice of medical therapy depends on the clinical presentation. Oral contraceptives are a good option when acne and hirsutism are the principal complaints. Adolescents with isolated cycle irregularity may be placed on a cyclical progestin regimen to induce withdrawal bleeding. Metformin, by decreasing insulin resistance, alleviates many of the hormonal disturbances and restores menses in a considerable proportion of patients. It may be used alone or in combination with oral contraceptives. Independently of medical treatment, restoration and maintenance of bodyweight within normal range is of paramount importance.
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PMID:Polycystic ovary syndrome in adolescents: current and future treatment options. 1703 48

Dehydroepiandrosterone and dehydroepiandrosterone-sulfate are precursors of androgens and estrogens, support the gonadal sexual steroid production. The levels of dehydroepiandrosterone and dehydroepiandrosterone-sulfate are maximal between the ages of 20 and 30 years, then start a decline of 2% per year, leaving a residual of 10-20% of the peak production by the eight decade of life. The age-associated decrease may lead to osteoporosis, deterioration of lipid-metabolism, cardiovascular diseases and second type of diabetes mellitus. Decreased levels were found in autoimmune diseases and in sexual dysfunction, too. Intracrinology describes the formation of active hormones which exert their action in the same cells where synthesis took place without release into the pericellular compartment. The high local androgen and estrogen concentration may be important in the pathomechanism of hirsutism, acne, seborrhea, breast and prostate cancer. Administration of dehydroepiandrosterone resulted in a reduction of postmenopausal osteoporosis, also the decreased symptoms in systemic lupus erythematosis, psychiatric diseases and sexual disfunction. The authors summarize the metabolism of dehydroepiandrosterone and dehydroepiandrosterone-sulfate and their role in different diseases.
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PMID:[Significance of dehydroepiandrosterone and dehydroepiandrosterone sulfate in different diseases]. 1740 38


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