Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0311277 (abdominal obesity)
 2,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin resistance syndrome and the polycystic ovary syndrome (PCOS) appear to have some following coincidences: the existence of subclinical acanthosis nigricans in PCOS hyperinsulinemic women, correlation of insulin levels and free testosterone, insulin-like growth factor I binding protein (IGFIBP), and sex-hormone binding globulin. Insulin and IGFI act synergically with luteinizing hormone increasing the activity of cytochrome P450c17 and its enzymatic activity in the adrenals. The decrease in IGFI level and IGFI receptors in the ovarian granulosa cells reduce the steroids aromatisation. The increased expression of IGFI receptors in the theca cells favours the androgens' synthesis. Long-term insulin therapy results in an increase in ovary volume and the blood androgens levels. The deterioration of insulin resistance in PSOC women progresses also by the reduction of type I of skeletal muscle fibres which are sensitive to insulin, and the increase of type II fibres which are resistant to insulin in hyperandrogenemia. Testosterone deteriorates the skeletal as well as hepatic insulin sensitivity by both its facilitating effect on lipolysis and the increase of free fatty acids. Abdominal obesity seen in PCOS and insulin resistance is composed by adipocytes with glucocorticoid receptors, which after cortisol stimulation activate the lipoprotein lipase and fat accumulation. Gynoid obesity with the preferential aromatisation of steroids is not evolved because of the low estrogens and progesterone levels in PCOS. Low progesterone levels (with anticortisol effect) support the development of abdominal obesity. Ultimately, the early peak of insulin secretion (4-8 min) in PCOS is higher. This fact should testify a certain diabetic disposition. (Ref. 37.)
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PMID:[The polycystic ovary syndrome and insulin resistance]. 949 Jan 71

Abdominal obesity has been suggested to be associated with perturbations of the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In a population of 51-yr-old men (n = 284) salivary cortisol concentrations were determined on repeated (n = 7) occasions over a random working day, and perceived stress was reported in parallel. Cortisol values were then related to reported stress (stress-related cortisol). A standardized lunch was used as a physiological challenge. A low dose (0.5 mg) dexamethasone suppression test was also performed as well as determinations of testosterone and insulin-like growth factor I (IGF-I). Body mass index [weight (kilograms)/height (meters)2]; waist/hip circumference ratio (WHR); sagittal trunk recumbent diameter (D); fasting insulin; blood glucose; triglycerides; and total, low density (LDL), and high density (HDL) lipoprotein cholesterol were also determined. Cortisol concentrations were highest in the morning, and lunch was followed by a peak (P = 0.044). Two types of diurnal cortisol curves were identified, one characterized by a high variability with high morning values, and another with low variability and low morning values. Both correlated strongly with suppression of salivary cortisol by dexamethasone (P < 0.001). Stress-related cortisol secretion was associated with D (P = 0.051), low IGF-I (P = 0.006), and diastolic blood pressure (P = 0.078). When the type of diurnal cortisol curve was taken into consideration by statistical weighting, stress-related cortisol secretion in subjects with high variability showed associations with testosterone (P < 0.001), D, total and LDL cholesterol, diastolic blood pressure (P < 0.001), fasting insulin (P = 0.039), and glucose (P = 0.030) as well as, negatively, triglycerides (P < 0.001). When weighted for a low variability of diurnal cortisol secretion, stress-related cortisol secretion showed strong negative relationships with IGF-I, testosterone, and HDL. Furthermore, strong, consistent relationships (all P < 0.001) were found with obesity factors (body mass index, WHR, and D), and with metabolic (insulin, glucose, triglycerides, and total and LDL cholesterol) as well as hemodynamic variables (systolic and diastolic blood pressure and heart rate). These results clearly show interactions between diurnal cortisol secretion related to perceived stress and anthropometric, endocrine, metabolic, and hemodynamic variables. This seems to occur with apparently normal regulation of the HPA axis (high morning peaks and variability as well as dexamethasone suppression of cortisol), where other endocrine variables are not affected. With a low diurnal cortisol variation and blunted dexamethasone suppression, indicating abnormal regulation of the HPA axis, perceived stress-dependent cortisol values were strongly related to perturbations of other endocrine axes as well as abdominal obesity with metabolic and hemodynamic abnormalities. Perturbations of the regulations of the HPA axis such as those described in combination with low dexamethasone suppressibility are known to follow long term overactivation of the axis by factors such as environmental stress.
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PMID:Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. 962 6

Perturbations in the sympathetic nervous system may be anticipated in adults with hypopituitarism and untreated GH deficiency, because the syndrome is associated with both peripheral and central factors known to modulate sympathetic traffic. The higher prevalence of hypertension and increased cardiovascular morbidity/mortality reported in GH-deficient patients may suggest increased activity of the sympathetic nervous system. We recorded muscle sympathetic nerve activity (MSNA) in 10 hypopituitary adults with adequate hormonal replacement therapy except GH and in 10 healthy controls matched for age, gender, and body mass index to test whether hormonal aberrations in hypopituitarism and untreated GH deficiency are associated with an increase in sympathetic nerve traffic. Blood samples for insulin-like growth factor I, free T4, and TSH were taken after an overnight fast, followed by an oral glucose tolerance test. Direct intraneural recordings of MSNA were performed with a tungsten microelectrode from the peroneal nerve. The hypopituitary subjects had markedly increased MSNA (54 +/- 4 bursts/min vs. 34 +/- 4 in controls; P < 0.002), which was not related to abdominal obesity or altered glucose metabolism. When assessed for the whole study group, MSNA was inversely correlated to serum insulin-like growth factor I (r = -0.59; P < 0.006) and TSH (r = -0.46; P < 0.04). MSNA was positively correlated to diastolic blood pressure (r = 0.80; P < 0.0005) in patients, but not in controls. The intense sympathetic discharge is suggested to be of central origin and may be an important underlying mechanism for the secondary hypertension and increased cardiovascular morbidity/mortality in this patient group.
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PMID:Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency. 962 13

Subjects with abdominal obesity show several signs of a perturbed regulation of the hypothalamic-pituitary-adrenal (HPA) axis. This is known to occur after chronic, submissive stress. Perceived environmental stress is depending on personality characteristics. Therefore, personality disorders (PD:s) were examined in relation to HPA axis status, other endocrine and metabolic variables as well as anthropometry. Men (no.=284) aged 51 years, recruited in similar subgroups of low, median and high waist/hip circumference ratio (WHR) from a sample of 1302 men. Measurements of personality disorders by Structured Clinical Interview for DSM-III-R, Axis II (SCID II), body mass index (BMI, weight, kg/height2, m2), WHR and abdominal sagittal diameter (D), dexamethasone suppression test (0.5 mg, salivary measurements of cortisol), insulin-like growth factor I (IGF-I), testosterone and metabolic variables. Men with cluster A (paranoid, schizotypal, schizoid) PD showed an increased BMI, WHR and D, independent of dexamethasone suppression. Testosterone was decreased in these men in relation to a blunted dexamethasone suppression. BMI, WHR and D were increased in men with cluster B (borderline, histrionic, narcissistic) and cluster C (avoidant, dependent, obsessive compulsive, passive aggressive) PD, only in relation to a blunted dexamethasone suppression. Furthermore, IGF-I was low in cluster B. Metabolic variables were differently associated to clusters of PD but generally followed obesity. Path-analytic models suggested that cluster B and C PD were followed by blunted dexamethasone suppression and obesity. Men with cluster A PD showed centralized body fat distribution, independently of dexamethasone suppression. In contrast, men with impulsive (cluster B) and anxious (cluster C) personality disorders seem often to have abdominal obesity only in combination with a blunted dexamethasone suppression test, suggesting a HPA axis disturbance. These results suggest that PD:s are involved in the development of abdominal obesity in men, with different endocrine and metabolic profiles depending on the type of PD. This might hypothetically be due to frequent exposure and/or an increased sensitivity to environmental stress factors, caused by aberrant personalities.
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PMID:Personality disorders in relation to anthropometric, endocrine and metabolic factors. 1034 62

Epidemiologic evidence suggests obese premenopausal women experience a reduced risk of breast cancer. The mechanism underlying this protection is not fully understood although it is well documented that abdominal obesity may impair ovulatory function and reduce gonadal steroidogenesis. We measured levels of several metabolic markers that are modified by obesity [measured by body mass index (BMI, (weight (kg)/height (m2)))] and play a role in the reproductive axis, including, leptin, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), C-peptide and prolactin in 233 cases and 251 controls participating in a retrospective study of breast cancer in young women conducted in the Seattle/Puget Sound region between 1990 and 1992. Consistent with the finding of a reduced risk with increasing BMI, risks declined with leptin levels, although to a lesser degree with odds ratios (OR) for the highest vs. lowest quartile of BMI=0.34 (95% C.I. 0.3-0.8) and for leptin=0.71 (95% C.I. 0.5-1.3). IGF-I, IGFBP3, C-peptide and prolactin were not related to breast cancer risk in a dose-dependent manner. With the possible exception of leptin, our findings do not suggest that these markers explain the breast cancer protection provided by obesity in premenopausal women.
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PMID:Interrelationships between serum leptin, IGF-1, IGFBP3, C-peptide and prolactin and breast cancer risk in young women. 1650 16

Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angiogenesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC.
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PMID:Metabolic syndrome and triple-negative breast cancer: a new paradigm. 2229 51

High serum levels of insulin-like growth factor I (IGF-I) are associated with an increased risk of sporadic breast cancer (BC). Furthermore, insulin and markers of insulin resistance, such as abdominal obesity, high blood glucose, high serum testosterone and metabolic syndrome, may affect both BC incidence and prognosis. We hypothesized that all these factors might be relevant also for hereditary BC, due to a deleterious mutation of BRCA genes. Epidemiological observation suggested that weight, energy intake (usually associated with higher bio-availability of growth factors) and physical activity may be relevant in BRCA mutation carriers. Mechanistic studies hypothesized a functional interaction between BRCA genes and the IGF-I system. We have provided some evidence that high serum levels of IGF-I are associated with a significantly increased penetrance. We are recruiting a larger cohort of BRCA mutation carriers in order to test potential modulators of penetrance and prognosis. Within this cohort, we have planned a randomized controlled trial to test whether moderate calorie and protein restriction, together with physical activity, decrease IGF-I. Eligible study subjects are women with or without BC, aged 18-70, with a proven deleterious BRCA mutation, and without metastases. All the women will receive recommendations for the dietary prevention of cancer. The women will be then randomized into an active life-style intervention group and into a control group that will receive only the baseline recommendations. We expect to significantly reduce IGF-I in the intervention group. This trial and the subsequent cohort follow-up might open up primary prevention options for genetic BC.
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PMID:A randomized controlled trial of diet and physical activity in BRCA mutation carriers. 2416 48