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 level of sex hormone-binding globulin (SHBG) is associated with glucose metabolism in nondiabetic women and men, and the finding of low SHBG levels is suggested to be a predictor of the development of type 2 (noninsulin-dependent) diabetes mellitus. To further assess the relationship between SHBG levels and glucose metabolism, we measured serum concentrations of sex hormones and SHBG in 23 well characterized diabetic men, and studied the relationship between these variables and parameters of glucose and lipid metabolism. Insulin sensitivity was estimated using the hyperinsulinemic euglycemic glucose clamp technique. There was a strong positive correlation between the level of SHBG and the sensitivity to insulin in these individuals (r = 0.74; P < 0.001), which was independent of obesity and abdominal fat accumulation. Controlling for the effect of fasting C-peptide and insulin levels did not change the correlation coefficient significantly. SHBG levels did not correlate with levels of free testosterone (F-T), free estradiol (F-E2), or F-T/F-E2 ratio. F-E2 was positively correlated with levels of diastolic blood pressure and triglycerides (r = 0.44; P < 0.05 and r = 0.62; P < 0.001, respectively). These findings support earlier observations that associate insulin resistance with levels of SHBG, and for the first time demonstrate a direct correlation between sensitivity to insulin and SHBG levels in men with type 2 diabetes.
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PMID:Level of sex hormone-binding globulin is positively correlated with insulin sensitivity in men with type 2 diabetes. 843 67

Insulin resistance, defined as a diminished effect of a given dose of insulin on glucose homeostasis, is a highly prevalent feature of women with PCOS. Insulin resistance in PCOS is closely associated with an increase in truncal-abdominal fat mass, elevated free fatty acid levels, increased androgens, particularly free testosterone through reduced SHBG levels, and anovulation. The causes for insulin resistance in PCOS are still unknown. One line of evidence suggests that an increase in truncal-abdominal fat mass and subsequently increased free fatty acid levels induce insulin resistance in women with PCOS. Increased effects of corticosteroids and a relative reduction in oestrogen and progesterone seem to be involved in the aberrant body fat distribution. Conversely, there are also results supporting primary, genetic target cell defects as a cause of insulin resistance in PCOS. An explanation for these seemingly contradictory results could be that the group of women with PCOS is heterogeneous with respect to the primary event in carbohydrate/insulin disturbances. Also insulin secretion in PCOS is characterized by heterogeneity. At one end of the spectrum is a large subgroup of mainly obese women with reduced insulin secretion, which appears to result from failure of the beta cells to compensate for insulin resistance in susceptible women, resulting in glucose intolerance and NIDDM. In the insulin-resistant patients with normal glucose tolerance, most of the hyperinsulinaemia is probably due to secondarily increased insulin secretion and decreased insulin degradation. However, a component of the increased first-phase insulin release is not due to measurable insulin resistance. Notably, this is also found in lean women with normal insulin sensitivity, and is not reversed after weight reduction, in contrast to the findings for insulin resistance. The implications of this enhanced insulin release are not fully clear, but it may tentatively be associated with carbohydrate craving and subsequently increased risks for development of obesity and insulin resistance. It may represent a primary disturbance of insulin secretion in PCOS or may be associated with the perturbed steroid balance in anovulation. The insulin-androgen connection in PCOS appears to be amplified by several different mechanisms, notably in both directions, the initiating event probably varying between individuals. Thus insulin increases the biological availability of potent steroids, primarily testosterone, through the suppression of SHBG synthesis. Insulin is also involved as a progonadotrophin in ovarian steroidogenesis, with the possible net result of interfering with ovulation and/or increasing ovarian androgen production in states of hyperinsulinaemia. Conversely, testosterone may indirectly contribute to insulin resistance through facilitating free fatty acid release from abdominal fat, but perhaps also through direct muscular effects at higher serum levels. It seems likely that this constitution, presumably genetic, would provide evolutionary advantages in times of limited nutrition, given the energy-saving effects of insulin resistance. Hypothetically, hyperinsulinaemia (primary) could provide a stimulus to ensure intake of nourishment, but unlimited food supplies could in some cases initiate a vicious 'anabolic' circle, in which several of the proposed amplifying mechanisms between insulin and androgens--in both directions--could take part.
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PMID:Disturbances in insulin secretion and sensitivity in women with the polycystic ovary syndrome. 877 46

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

This study examined the relationship of hepatic and peripheral insulin sensitivity and beta-cell secretory function with serum sex hormone-binding globulin (SHBG) in men and women with Type 2 diabetes mellitus (DM). Fasting insulin, glucose and SHBG were measured in 58 Type 2 diabetic patients of both sexes (36 men) who were on diet treatment only and terms for insulin sensitivity and beta-cell secretion obtained by modelling. There was no significant difference in SHBG between men and women despite similar degree of obesity. SHBG was positively correlated (r = 0.41, p < 0.01) to hepatic insulin sensitivity derived from mathematical modelling of fasting glucose and insulin data using the homeostasis assessment model (HOMA). This relationship was independent of gender (men, r = 0.48, p < 0.01; women, r = 0.45, p < 0.05). Fasting insulin correlated negatively with SHBG in men (r = -0.34, p < 0.05). There were also significant negative correlations between SHBG and either plasma glucose (r = -0.29, p < 0.05) or body mass index (r = -0.34, p < 0.05). SHBG did not correlate with HOMA-modelled beta-cell function. In a multiple regression analysis, SHBG was independently correlated only with insulin sensitivity (p < 0.05). Further studies in 15 of the diabetic patients (11 men), showed a significant positive correlation (r = 0.52, p < 0.05) between SHBG and peripheral insulin sensitivity derived by continuous infusion of glucose with model assessment (CIGMA) but not between SHBG and CIGMA-modelled beta-cell function. These results indicate that both hepatic and peripheral insulin sensitivity are similarly related to serum SHBG in Type 2 diabetes of both sexes. The sex-difference in SHBG was abolished in the patients.
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PMID:Serum sex-hormone-binding globulin is related to hepatic and peripheral insulin sensitivity but not to beta-cell function in men and women with Type 2 diabetes mellitus. 963 21

Men with low testosterone concentrations are usually hypogonadal. However, because variations in the testosterone transport protein, sex hormone-binding globulin (SHBG), directly influence the total testosterone concentration, confirmation of a low testosterone with a measurement of free testosterone or "bioavailable" testosterone (BAT) is recommended. In the present study, we examined the relationship of SHBG with free testosterone (Coat-A-Count assay, Diagnostic Products) and with BAT in men (n = 29) and women (n = 28) who participated in a study of the metabolic determinants of body composition. As expected, total testosterone was strongly positively correlated with SHBG among men (r = 0.68; P <0.01). Although the BAT was independent of SHBG in men (r = 0.02), SHBG was an important predictor of free testosterone (r = 0.62; P <0.01). In contrast, in women serum concentrations of total testosterone (r = -0.26; P = 0.17), free testosterone (r = -0.30; P = 0.17), and BAT (r = -0.46; P = 0.013) all tended to be lower with increasing SHBG. Free testosterone was nearly perfectly positively correlated with total testosterone (r = 0.97) in men, among whom free testosterone represented a relatively constant percentage of the total testosterone (0.5-0.65%), and the percentage of free testosterone was unrelated to SHBG. Thus the Coat-A-Count free testosterone concentration in men, like the total testosterone concentration, is determined in part by plasma SHBG. Accordingly, androgen deficiency may be misclassified with this assay in men with low SHBG. Moreover, the previous findings of reduced free testosterone concentrations with hypertension or hyperinsulinemia or as a risk factor for developing type 2 diabetes, conditions in which SHBG is reduced, may have been methodology-related.
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PMID:The analog free testosterone assay: are the results in men clinically useful? 1022 85

Almost two decades of research have greatly increased our knowledge in the complex field of metabolic aberrations in polycystic ovary syndrome, but still many problems remain unsolved. The statistical association between insulin levels and androgens originally put the focus on possible direct cause-and-effect relationships between these factors. Indeed there is evidence that insulin may affect ovarian functions in multiple ways, presumably in some cases causing anovulation and hyperandrogenism. Clearly, insulin may increase biologically active testosterone through reducing SHBG levels. Conversely, major increases in androgen levels may induce muscular changes leading to reduced insulin-mediated glucose uptake. There are suggestions of increased steroidogenesis in both ovarian and adrenal pathways, with the net result of increased androgen production. There are also findings supporting increased corticosteroid production, which could contribute to insulin resistance directly or through promoting accumulation of abdominal fat, a typical feature of over-weight women with PCOS. Free fatty acids, released in great amounts from abdominal fat, may induce insulin resistance. Insulin resistance may also be due to a primary aberration in the insulin receptor. Putatively increased serine phosphorylation may cause both impairment of the insulin signal and increased 17,20 lyase activity, thus suggesting a common cause for insulin resistance and increased androgen production. There are also findings supporting a high prevalence of beta-cell dysfunction in PCOS, ranging from increased insulin secretion, not explained by insulin resistance or BMI, to failing beta-cell function, mainly in obese women during progress to glucose intolerance and NIDDM. Recent genetic findings also support a multifactorial genesis to PCOS, notably with positive findings both in genes regulating steroidogenesis and insulin secretion. It is suggested that PCOS is the result of "thrifty" genes, providing advantages in times of shortage of nutrition such as muscular strength, moderate abdominal fatness and decreased insulin sensitivity, i.e. an anabolic, energy saving constitution. However, when this constitution is exposed to unlimited food supplies and modern sedentary life style a full-blown PCOS with insulin resistance and infertility is triggered, presumably via several mechanisms, which follow a logical amplification system between two basic anabolic hormones, insulin and testosterone.
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PMID:Polycystic ovary syndrome and insulin resistance: thrifty genes struggling with over-feeding and sedentary life style? 985 13

Many adolescents present with hirsutism and irregular menses. The challenge for the clinician is to distinguish physiologic anovulatory cycles from true menstrual disorders such as PCOS, and to differentiate PCOS from other causes of hyperandrogenism in hirsute adolescents. Common clinical features seen in adolescents with PCOS include hirsutism, acne, menstrual irregularity, and obesity. Biochemical abnormalities include hyperandrogenism, acyclic estrogen production, LH hypersecretion, decreased levels of SHBG, and hyperinsulinemia. Management strategies for a patient with PCOS include treatment of features which may cause distress to the adolescent, such as hirsutism, acne, and irregular menses, and prevention of long-term sequelae. Oral contraceptive pills, antiandrogens, and cosmetic treatments are used to treat hirsutism, acne, and menstrual irregularity. Oral contraceptive pills or medroxyprogesterone acetate are given to prevent endometrial hyperplasia and carcinoma. Counseling about weight loss and nutrition are essential, as weight loss may improve signs of hyperandrogenism and menstrual irregularity and may prevent NIDDM and cardiovascular disease. Insulin-sensitizing agents show promise in terms of decreasing hyperandrogenism, restoring ovulatory cycles, treating infertility, and preventing long-term sequelae. Finally, it is important to recognize that adolescents with PCOS may experience psychological distress because of the clinical manifestations of hyperandrogenism or when confronted with the information that they have a chronic illness. Psychological support should be available for these young women. Future research is likely to further elucidate the pathophysiology of PCOS, identify candidate genes, and clarify which adolescents are at risk for long-term sequelae. Prospective studies are needed to identify which therapies could potentially reduce the risk of infertility, diabetes, cardiovascular disease, and endometrial carcinoma in young women with PCOS.
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PMID:Polycystic ovary syndrome. 1037 Jul 13

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

In humans, steroid hormones circulate in the blood mainly bound to specific steroid transport proteins, namely corticosteroid-binding globulin (CBG) for cortisol and sex hormone-binding globulin (SHBG) for testosterone and estradiol. The binding activities of these proteins are believed to modulate the biodisposal of steroids to target cells. It has been shown in vitro that insulin is a potent inhibitor of both CBG and SHBG secretion by a human hepatoblastoma cell (HepG2) line. To further investigate this potential effect of insulin in vivo, we prospectively studied three groups of lean subjects, obese subjects, and obese subjects with glucose intolerance, all of whom were otherwise healthy. The three groups were comparable in sex and age, and in the two obese groups, body mass index, waist to hip ratio, and blood pressure were similar. Plasma total CBG concentrations (38.2 +/- 5.4 vs. 31.7 +/- 4.05 mg/L; P = 0.016) and glycosylated CBG levels (37.3 +/- 5.2 vs. 31 +/- 3.9 mg/L; P = 0.018) were significantly increased in obese subjects with glucose intolerance. Plasma CBG correlated positively with fasting glucose levels (r = 0.49; P = 0.002), hemoglobin A1c levels (r = 0.35; P = 0.03), and area under the curve of glucose after an oral glucose tolerance test (r = 0.45; P = 0.005) and correlated negatively with the insulin response to i.v. glucose (AIRg; -0.38, P = 0.02) as well as to oral glucose (r = -0.40; P = 0.01) challenge tests. CBG levels did not covariate with insulin sensitivity. Multiple linear regression analysis showed that only AIRg contributed to the variability of the CBG concentration (P = 0.03), explaining 41% of its variance. Morning cortisol levels did not differ between the groups and did not correlate to any of the glucose or insulin metabolism parameters. Because carbohydrate chains influence the biological activity and half-life of glycoproteins, we analyzed the migration profile of CBG by Western blot and the interaction of CBG with lectin, Con A. The results indicated that the CBG mol wt and interaction with Con A did not differ between lean and obese patients. These data favor the hypothesis that the inhibitory effect of insulin on CBG liver secretion might be relevant in vivo and therefore contribute to decrease CBG levels in obese patients with enhanced insulin secretion. In both men and women, SHBG levels correlated negatively with fasting glucose (r = -0.55; P < 0.0001) and hemoglobin A1c (r = -0.38; P = 0.02) and positively with insulin sensitivity (S(I); r = 0.65; P = 0.003 and r = 0.63; P = 0.007 in men and women, respectively), but not with insulin secretion. The disposition index (S(I) x AIRg) was significantly decreased in the obese, glucose-intolerant subjects, suggesting that AIRg was inadequate for their degree of insulin resistance. The disposition index correlated positively with plasma SHBG levels (r = 0.52; P = 0.001) and negatively with plasma CBG levels (r = -0.54; P = 0.001). Our data suggest that CBG is a marker of insulin secretion in a similar way as SHBG is a marker of insulin sensitivity. As high plasma CBG levels have been associated with increased incidence of type 2 diabetes, this important issue merits further investigations.
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PMID:Plasma total and glycosylated corticosteroid-binding globulin levels are associated with insulin secretion. 1048 86

An association between sex hormone-binding globulin (SHBG) and insulin resistance expressed by the homeostasis model (HOMA-R), and the significance of both variables as risk factors for the development of type 2 diabetes were investigated in 483 Japanese-American subjects. The serum SHBG level was significantly higher in women (68.7 nmol/l) than in men (45.1 nmol/l). This difference was also significant independently of age, body mass index (BMI), waist to hip ratio (WHR), and HOMA-R. When multiple regression analysis was performed after adjustment for age and BMI, SHBG was not correlated with HOMA-R in men. In women, SHBG was not significantly correlated with HOMA-R after adjustment for age, BMI, and WHR. In a 3-year prospective analysis, HOMA-R was significantly higher in converters to type 2 diabetes than non-converters in both men and women which was independent of age, BMI and WHR. However, after adjusting these variables, SHBG was not a significant risk factor either in men or women. These results indicate that SHBG might be related to insulin resistance secondarily via BMI and/or WHR in both men and women among Japanese-Americans. HOMA-R is a useful index for both men and women as a risk factor of type 2 diabetes when only fasting blood samples can be obtained.
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PMID:Association of sex hormone-binding globulin and insulin resistance among Japanese-American subjects. 1066 Feb 23


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