UMLS:C0011860 - FACTA Search

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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High free fatty acid (FFA) levels are common in obesity and in diseases such as diabetes that are associated with the obese state. Dehydroepiandrosterone (DHEA) decreases dietary fat consumption, body fat content, and insulin levels in the obese Zucker rat (ZR), a genetic model of human youth-onset obesity and type 2 diabetes mellitus. This study was conducted to investigate the effects of DHEA on lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and serum FFA levels. Because DHEA is known to decrease fat consumption and body fat, we postulate that DHEA may also alter FA profiles and FFA levels of the obese ZR such that they more closely resemble the profiles and levels of their lean siblings. In this study there was a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6% DHEA, and PF groups were given the same average calories consumed by their corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA profiles and FFA levels were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean rats (approximately 0.6 mmol/L). After 30 d of DHEA treatment, FFA levels were lower (P < 0.05) in both lean and obese groups. Although several significant differences in FA profile of serum, hepatic, and adipose lipid components were observed between lean and obese ZR, DHEA-related changes were only observed in the serum phospholipid (PL) and liver PL and triglyceride fractions. The slight but significant decrease in serum FFA levels may be reflected by changes in serum PL FA profiles. Specific hepatic FA profile alterations may be related to DHEA's known effects in inducing hepatic peroxisomes. We speculate that such FA changes may give insight into a mechanism for the action of DHEA.
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PMID:Dehydroepiandrosterone alters lipid profiles in Zucker rats. 1090 22

Lower androgen levels have been suggested to be associated with type 2 diabetes and central obesity and are probably involved into the development of atherosclerosis. The present study investigates the effect of acute and chronic exercise on Dehydroepiandrosterone (DHEA) levels in relation to abdominal fat distribution and metabolic status in type 2 diabetes. Twenty weight-stable, middle-aged males with type 2 diabetes were enrolled in the study and participated in a submaximal (VO(2) peak) and moderate (50% VO(2) peak) exercise bout. The subjects were randomly assigned either to a trained or a control group, respectively. Physical training consisted of an 8 week program of aerobic exercise (75% VO(2) peak, 45 min), twice a week and intermittent exercise, once a week, on a bicycle ergometer. Acute exercise significantly increased DHEA and Testosterone (T) levels. Physical training increased VO(2) peak (42%, p <0.001), insulin sensitivity index (K(ITT) ) (57.5%, p <0.02), and basal DHEA levels (36%, p <0.05), and decreased HbA1c (29%, p <0.001), visceral adipose tissue (VAT) (44%, p <0.01) and subcutaneous adipose tissue (SAT) levels (18%, p <0.01). Body weight, BMI and insulin, T levels were not modified. Changes in DHEA levels were not correlated with changes in insulin sensitivity and abdominal fat distribution. In conclusion, exercise training favourably affects DHEA levels independently of improvements of metabolic status and abdominal fat distribution in patients with type 2 diabetes.
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PMID:Effects of a single bout of exercise and exercise training on steroid levels in middle-aged type 2 diabetic men: relationship to abdominal adipose tissue distribution and metabolic status. 1117 15

Hypoandrogenemia is frequently associated with hyperinsulinemia in men with the metabolic syndrome. We questioned whether insulin or changes in blood glucose levels influence pituitary gonadotropin secretion or testicular steroidogenesis in healthy men. Also, the relationship between hypoglycemia-induced activation of the hypothalamus-pituitary-adrenal axis and altered steroidogenesis was examined. Euglycemic and hypoglycemic clamp experiments were performed in 30 healthy men over a period of 6 h. Half of the men were infused with insulin at a rate of 1.5 mU/min.kg; the other half were infused at a rate of 15.0 mU/min.kg. Plasma glucose was held constant during a euglycemic clamp session and was decreased stepwise in a hypoglycemic clamp session. LH and total/free T concentrations decreased under hypoglycemic conditions regardless of the rate of insulin infusion. With euglycemic conditions, LH and T levels remained unchanged. Dehydroepiandrosterone concentrations increased during hypoglycemia, but not during the euglycemic conditions. The FSH concentration was not affected by insulin or glycemic clamps. Hypoglycemia acutely suppresses T secretion, and this effect is apparently mediated by pituitary LH. Insulin is ineffective. As counterregulation to hypoglycemia begins at normoglycemic ranges in poorly controlled type 2 diabetes and probably also in patients with long-term perturbed glucose regulation in the metabolic syndrome, control of glucose-responsive neurons in the brain may contribute to hypoandrogenemia. Apart from down-regulation of hypothalamic release of GnRH, concurrent activation of the pituitary-adrenal axis (i.e. increased release of dehydroepiandrosterone) may add to the suppressive effect of hypoglycemia on gonadal steroidogenesis.
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PMID:Hypoglycemia, but not insulin, acutely decreases LH and T secretion in men. 1160 May 62

Insulin-resistant muscle tissue contains low proportions of arachidonic acid (AA), and increased proportions of muscle AA correlate with improved insulin sensitivity. Dehydroepiandrosterone (DHEA) and AA, like the thiazolidinedione drugs that decrease insulin resistance (IR), are peroxisome proliferators. Long-chain fatty acids (FA) have been named the "one true" endogenous ligand for activating the peroxisome proliferator-activator receptor (PPAR), and DHEA has been named a "good candidate" as a naturally occurring indirect activator of PPAR. This study was conducted to determine DHEA's effects on lipid profiles of skeletal and cardiac muscle in lean and obese Zucker rats (ZR), a model of IR, type 2 diabetes mellitus, and obesity. We hypothesize that DHEA may alter long-chain FA profiles in muscle tissue of obese rats such that they more closely resemble that of the lean. In our experiments, we employed a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. For 30 d, the diet of the two DHEA groups was supplemented with 0.6% DHEA; PF groups were given the average daily calories consumed by their corresponding treatment group. Hearts and gastrocnemius muscles were assayed for phospholipid (PL), free FA, and triglyceride (TG) FA profiles. The proportion of PL AA was significantly greater in both muscle types of lean compared to obese rats. Hearts from both DHEA groups had greater PL proportions of AA and less oleic (18:1) acid than their PF controls. Likewise, 18:1 proportions were significantly lower in the gastrocnemius; however, AA proportions were not significantly different. Similar phenotypic profile differences were observed in the TG fraction of both muscle types. There were no DHEA-related TG FA profile alterations.
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PMID:Dehydroepiandrosterone alters phospholipid profiles in Zucker rat muscle tissue. 1183 92

Clinical characteristics of PCOS Syndrome Two fundamental characteristics: hyperandrogenism and anovulation which lead to hirsutism and oligo-or amenorrhea. Other features include obesity, acanthosis nigricans, and metabolic disruption (insulin resistance with hyperinsulinemia, glucose intolerance, or type II diabetes mellitus). Complementary tests Serum testosterone and DHEA-S levels: to exclude androgen-producing tumors. Serum 17-hydroxyprogesterone level: to exclude congenital adrenal hyperplasia, 21-hydroxylase deficiency. Ultrasound: increased size of the ovaries and central stroma with presence of peripheral follicular cysts (8-10) measuring about 8 mm in diameter. Pathophysiology Therapeutic approaches Therapeutic approaches
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PMID:[Polycystic ovaries in 2001: physiology and treatment]. 1198 85

An increase in androgenicity may contribute to the development of insulin resistance in postmenopausal women. Increased androgenicity in women has been found to be associated with the development of type 2 diabetes. In addition, obesity and central obesity are associated with greater androgenicity. Insulin sensitivity, androgenicity, and body composition were characterized in 34 nondiabetic postmenopausal women age 72 +/- 1 years (mean +/- SEM) to test the hypothesis that androgenicity is a predictor of insulin sensitivity independent of measures of obesity. Androgenicity was measured using levels of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and free androgen index (FAI). Insulin sensitivity (S(I)) was determined from a frequently sampled intravenous glucose tolerance test. Body composition measures included body mass index (BMI) and dual energy x-ray absorptiometry measurements of total and central fat mass. S(I) was found to be associated with total fat mass (r = -.51, P =.002), central fat mass (r = -.62, P =.0001), BMI (r = -.55, P =.0008), SHBG levels (r =.65, P =.0001), and FAI (r = -.41, P =.01). SHBG levels were inversely correlated with central fat mass (r = -.59, P =.0002). Using multiple regression, SHBG and central fat mass were the only significant independent predictors of S(I), accounting for 50% of its variance (r =.71, P =.0001); total fat mass, BMI, total and free testosterone, DHEA-S, androstenedione, and FAI did not enter the model. We conclude that there is a significant association between insulin sensitivity and androgenicity in postmenopausal women that is independent of obesity. Interventions to decrease androgenicity may therefore be useful in improving insulin sensitivity in postmenopausal women.
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PMID:Androgenicity and obesity are independently associated with insulin sensitivity in postmenopausal women. 1504

n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), mainly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), are present in mammal tissues both from endogenous synthesis from desaturation and elongation of 18:3 n-3 and/or from dietary origin (marine products and fish oils). In rodents in vivo, n-3 LC-PUFA have a protective effect against high fat diet induced insulin resistance. Such an effect is explained at the molecular level by the prevention of many alterations of insulin signaling induced by a high fat diet. Indeed, the protective effect of n-3 LC-PUFA results from the following: (a) the prevention of the decrease of phosphatidyl inositol 3' kinase (PI3 kinase) activity and of the depletion of the glucose transporter protein GLUT4 in the muscle; (b) the prevention of the decreased expression of GLUT4 in adipose tissue. In addition, n-3 LC-PUFA inhibit both the activity and expression of liver glucose-6-phosphatase which could explain the protective effect with respect to the excessive hepatic glucose output induced by a high fat diet. n-3 LC-PUFA also decrease muscle intramyofibrillar triglycerides and liver steatosis. This last effect results on the one hand, from a decreased expression of lipogenesis enzymes and of delta 9 desaturase (via a depleting effect on sterol response element binding protein 1c (SREBP-1c). On the other hand, n-3 LC-PUFA stimulate fatty acid oxidation in the liver (via the activation of peroxisome proliferator activated receptor alpha (PPAR-alpha)). In patients with type 2 diabetes, fish oil dietary supplementation fails to reverse insulin resistance for unclear reasons, but systematically decreases plasma triglycerides. Conversely, in healthy humans, fish oil has many physiological effects. Indeed, fish oil reduces insulin response to oral glucose without altering the glycaemic response, abolishes extraggression at times of mental stress, decreases the activation of sympathetic activity during mental stress and also decreases plasma triglycerides. These effects are encouraging in the perspective of prevention of insulin resistance but further clinical and basic studies must be designed to confirm and complete our knowledge in this field.
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PMID:N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? 1546 Jan 68

DHEA (dehydroepiandrosterone) replacement is not part of the current standard of care in hypoadrenal subjects. Animal studies have shown that DHEA administration prevents diabetes. To determine the physiological effect of DHEA replacement on insulin sensitivity in adrenal-deficient women, we performed a single-center, randomized, double-blind, placebo-controlled, crossover study in 28 hypoadrenal women (mean age 50.2 +/- 2.87 years) who received a single 50-mg dose of DHEA daily or placebo. After 12 weeks, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. DHEA replacement significantly increased DHEA-S (sulfated ester of DHEA), bioavailable testosterone, and androstenedione and reduced sex hormone-binding globulin levels. Fasting plasma insulin and glucagon were lower with DHEA (42 +/- 4.94 vs. 53 +/- 6.58 pmol/l [P = 0.005] and 178 +/- 11.32 vs. 195.04 +/- 15 pmol/l [P = 0.02], respectively). The average amount of glucose needed to maintain similar blood glucose levels while infusing the same insulin dosages was higher during DHEA administration (358 +/- 24.7 vs. 320 +/- 24.6 mg/min; P < 0.05), whereas endogenous glucose production was similar. DHEA also reduced total cholesterol (P < 0.005), triglycerides (P < 0.011), LDL cholesterol (P < 0.05), and HDL cholesterol (P < 0.005). In conclusion, replacement therapy with 50 mg of DHEA for 12 weeks significantly increased insulin sensitivity in hypoadrenal women, thereby suggesting that DHEA replacement could have a potential impact in preventing type 2 diabetes.
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PMID:Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. 1573 54

We recently found that serum dehydroepiandrosterone sulfate (DHEA-S) concentration correlated inversely with the degree of urinary albumin excretion in a cross-sectional study. We therefore performed an observational study to investigate the relationship between serum DHEA-S concentrations and changes in urinary albumin excretion in male patients with type 2 diabetes to answer the question as to whether DHEA is a causal rather than simply coincidental intermediate linking urinary albumin excretion to cardiovascular disease (CVD). The relationship between serum DHEA-S concentration and changes in urinary albumin excretion was investigated in 207 consecutive male patients with type 2 diabetes. Baseline serum DHEA-S concentration and urinary albumin excretion were measured in 2003. After 12 months, urinary albumin excretion was measured and any changes in urinary albumin excretion were calculated. Patients were divided into tertiles according to DHEA-S concentration. Greater changes in urinary albumin excretion were seen in patients with low DHEA-S concentration (29.6+/-7.6mg/g creatinine) than in patients with high DHEA-S concentration (5.1+/-3.6mg/g creatinine, P=0.0091). An inverse correlation was observed between serum DHEA-S concentration and changes in urinary albumin excretion (r=-0.193, P=0.0052). Multiple regression analysis demonstrated that HbA1c (beta=0.241, P=0.0009), and serum DHEA-S concentration (beta=-0.195, P=0.0054) were independent determinants of changes in urinary albumin excretion. In conclusion, serum DHEA-S concentration was inversely correlated with changes in urinary albumin excretion, which may indicate causality in the increased CVD mortality in male patients with type 2 diabetes and low DHEA-S concentration.
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PMID:Low serum dehydroepiandrosterone sulfate concentration is a predictor for deterioration of urinary albumin excretion in male patients with type 2 diabetes. 1641 43

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

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