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)

Adiponectin is a novel adipocyte-specific protein, which, it has been suggested, plays a role in the development of insulin resistance and atherosclerosis. Although it circulates in high concentrations, adiponectin levels are lower in obese subjects than in lean subjects. Apart from negative correlations with measures of adiposity, adiponectin levels are also reduced in association with insulin resistance and type 2 diabetes. Visceral adiposity has been shown to be an independent negative predictor of adiponectin. Thus, most features of the metabolic syndrome's negative associations with adiponectin have been shown. Adiponectin levels seem to be reduced prior to the development of type 2 diabetes, and administration of adiponectin has been accompanied by lower plasma glucose levels as well as increased insulin sensitivity. Furthermore, reduced expression of adiponectin has been associated with some degree of insulin resistance in animal studies indicating a role for hypoadiponectinaemia in relation to insulin resistance. The primary mechanisms by which adiponectin enhance insulin sensitivity appears to be through increased fatty acid oxidation and inhibition of hepatic glucose production. Adiponectin levels are increased by thiazoledinedione treatment, and this effect might be important for the enhanced insulin sensitivity induced by thiazolidinediones. In contrast, adiponectin levels are reduced by pro-inflammatory cytokines especially tumour necrosis factor-alpha. In summary, adiponectin in addition to possible anti-inflammatory and anti-atherogenic effects appears to be an insulin enhancer, with potential as a new pharmacologic treatment modality of the metabolic syndrome and type 2 diabetes.
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PMID:Adiponectin: action, regulation and association to insulin sensitivity. 1565 35

Adiponectin, predominantly synthesized in the adipose tissue, seems to have substantial anti-inflammatory properties and to be a major modulator of insulin resistance and dyslipidemia, mechanisms that are associated with an increased atherosclerotic risk in diabetic patients. However, it is unknown whether higher levels of adiponectin are associated with a reduced risk for coronary heart disease (CHD) among diabetic individuals. We investigated the association between plasma adiponectin levels and incidence of CHD among 745 men with confirmed type 2 diabetes in the Health Professionals Follow-up Study. Participants were aged 46-81 years and were free of diagnosed cardiovascular disease at the time of blood draw in 1993/1994. During an average of 5 years of follow-up (3,980 person-years), we identified 89 incident cases of CHD (19 myocardial infarction and 70 coronary artery bypass surgery), confirmed by medical records. Levels of adiponectin were inversely associated with BMI and directly associated with age, alcohol intake, and duration of diabetes (P < 0.05). After adjustment for age, BMI, smoking, alcohol consumption, duration of diabetes, and other lifestyle factors, adiponectin was associated with a decreased risk for CHD events. The multivariate relative risk for CHD for a doubling of adiponectin was 0.71 (95% CI 0.53-0.95). Further adjustment for HDL cholesterol attenuated this association (0.78 [0.57-1.06]). The inverse association between adiponectin and CHD was consistent across strata of aspirin use, family history of myocardial infarction, alcohol consumption, insulin use, duration of diabetes, and levels of HbA(1c), triglycerides, C-reactive protein, and HDL cholesterol. Our study suggests that increased adiponectin levels are associated with a moderately decreased CHD risk in diabetic men. This association seems to be mediated in part by effects of adiponectin on HDL cholesterol levels.
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PMID:Adiponectin and future coronary heart disease events among men with type 2 diabetes. 1567 12

Adiponectin is a recently discovered adipocytokine that correlates negatively with body mass index and body fat. In patients with GH deficiency, treatment with recombinant human growth hormone (rhGH) reduces body fat mass and thus may also have a favorable effect in patients with metabolic syndrome, and would also be expected to increase adiponectin levels. However, due to its diabetogenic effect, rhGH treatment also bears an increased risk for the development of type 2 diabetes mellitus. We conducted a 18-month randomized, double-blind, placebo-controlled study to assess the effect of rhGH in combination with metformin (MGH) in 14 obese men (7 MGH; 7 Metformin+Placebo, 54 +/- 2 years, BMI 33.0 +/- 1.2 kg/m(2)) with mildly elevated fasting plasma glucose (FPG) at screening (6.1-8.0 mmol/l). All patients received metformin (850 mg twice daily) for treatment of type 2 diabetes mellitus/impaired glucose tolerance, either alone or in combination with rhGH (daily dose 9.5 mug/kg body weight). Glucose disposal rate (GDR) was measured using the euglycemic hyperinsulinemic clamp technique, and body composition was measured by DEXA at 0 and 18 months. After 18 months, the mean adiponectin concentration increased by 32 +/- 11 % (p = 0.018) in the MGH group and did not change in the MP group (- 10 +/- 13 %; p = n. s.). The difference in relative changes in adiponectin levels between the two groups after 18 months was statistically significant (p = 0.026). Improvement in insulin sensitivity (GDR) correlated positively with adiponectin levels (r = 0.73; p = 0.004). In conclusion, the additional administration of rhGH increased adiponectin levels in patients with metabolic syndrome, indicating its potential role in adiponectin-associated insulin sensitivity alterations.
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PMID:Effects of a combination of rhGH and metformin on adiponectin levels in patients with metabolic syndrome. 1570 40

Adiponectin is an adipose tissue-specific protein with insulin-sensitizing and antiatherogenic properties. Therefore, the adiponectin gene is a promising candidate gene for type 2 diabetes. We investigated the single nucleotide polymorphisms (SNPs) +45T/G and +276G/T of the adiponectin gene as predictors for the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial, which aimed to investigate the effect of acarbose compared with placebo on the prevention of type 2 diabetes. Compared with the TT genotype, the G-allele of SNP +45 was associated with a 1.8-fold risk for type 2 diabetes (95% CI 1.12-3.00, P = 0.015) in the placebo group. Subjects treated with placebo and simultaneously having the G-allele of SNP +45 and the T-allele of SNP +276 (the risk genotype combination) had a 4.5-fold (1.78-11.3, P = 0.001) higher risk of developing type 2 diabetes compared with subjects carrying neither of these alleles. Women carrying the risk genotype combination had an especially high risk of conversion to diabetes (odds ratio 22.2, 95% CI 2.7-183.3, P = 0.004). In conclusion, the G-allele of SNP +45 is a predictor for the conversion to type 2 diabetes. Furthermore, the combined effect of SNP +45 and SNP +276 on the development of type 2 diabetes was stronger than that of each SNP alone.
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PMID:The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. 1573 70

We studied the correlation between the adiponectin-leptin (A/L) ratio and parameters of insulin resistance in 220 Japanese patients with type 2 diabetes (138 men and 82 women). Body mass index (BMI), triglycerides (TGs), HDL cholesterol (HDL), and preheparin serum lipoprotein lipase (LPL mass) were examined as laboratory parameters of the insulin resistance. The correlations between these laboratory parameters and adiponectin, leptin, or A/L ratio were studied. Adiponectin levels correlated significantly with BMI (r = -0.298, P = .0003), TGs (r = -0.221, P = .0092), HDL (r = 0.31, P = .0002), and LPL mass (r = 0.26, P = .0021) in men, and with TGs (r = -0.29, P = .0093), HDL (r = 0.239, P = .0338), and LPL mass (r = 0.499, P < .0001) in women. Leptin levels correlated significantly with only BMI (r = 0.31, P = .0002) in men, and with BMI (r = 0.71, P < .0001) and TGs (r = 0.26, P = .0201) in women. Adiponectin and leptin levels tended to correlate with these parameters in an opposite manner. On the other hand, A/L ratio significantly correlated with BMI (r = -0.4, P < .0001), TG (r = -0.199, P = .0192), HDL (r = 0.235, P = .0054), and LPL mass (r = 0.244, P = .0390) in men, and with BMI (r = -0.482, P < .0001), TG (r = -0.402, P = .0002), HDL (r = 0.358, P = .0011), and LPL mass (r = 0.487, P < .0001) in women. Next, the patients were divided into 3 groups classified by their fasting plasma glucose (FPG) level, and the correlations between the parameters and A/L ratio or homeostasis model assessment (HOMA-R), and the correlation between A/L ratio and HOMA-R were investigated in each group. Significant correlations between the parameters and A/L ratio were tended to be observed as the FPG level rose; however, the significant correlations between the parameters and HOMA-R were no longer seen as FPG level elevated. The results suggested that the A/L ratio was effective in relevance as a parameter of insulin resistance to adiponectin or leptin alone, and a more sensitive and reliable marker of insulin resistance than HOMA-R as the FPG level elevated, in patients with type 2 diabetes.
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PMID:Correlation between the adiponectin-leptin ratio and parameters of insulin resistance in patients with type 2 diabetes. 1573 3

Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-alpha, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti-inflammatory effect. In this study, the relationship between fasting plasma adiponectin concentration and adiposity, body composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting insulin concentration were examined in Korean type 2 diabetes. The difference in the adiponectin concentrations was also examined in diabetic and non-diabetic subjects, with adjustment for gender, age and body mass index. 102 type 2 diabetics and 50 controls were examined. After a 12-h overnight fast, all subjects underwent a 75 gram oral glucose tolerance test. Baseline blood samples were drawn for the determinations of fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. The body composition was estimated using a bioelectric impedance analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the fasting adiponectin concentrations were significantly lower in men than in women. They were negatively correlated with BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r= -0.233). In addition, they were positively correlated with systolic blood pressure (r=0.321) and HDL-cholesterol (r= 0.291). The systolic blood pressure and HDL-cholesterol were found to be independent variables, from a multiple logistic regression analysis, which influenced the adiponectin concentration. Compared with the non-diabetic group, the adiponectin concentrations were significantly lower in the diabetic group, with the exception of obese males. In conclusion, the plasma adiponectin concentrations were closely related to the insulin resistance parameters in Korean type 2 diabetic patients.
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PMID:Plasma adiponectin and insulin resistance in Korean type 2 diabetes mellitus. 1574 4

The effect of short-term bezafibrate (BF) administration over time on the expression of adiponectin mRNA in the tissues was examined in Otsuka Long Evans Tokushima Fatty (OLETF) rats. Eight-week-old rats were divided into the high-dose (100 mg/kg) BF group (n=15), the low-dose (10 mg/kg) BF group (n=15), or the control group (n=15) and followed up for 14 d. Tri-glyceride and free fatty acid levels significantly decreased in a dose-dependent manner in the high-dose BF group. The insulin levels increased with time, although they were significantly lower in the high-dose BF group on d 3 and 7 than the control group. Adiponectin levels significantly increased in the high-dose BF group. On d 14 of BF administration, the levels of VLDL and chy-lomicron were significantly lower in BF groups, and adiponectin mRNA expression in the white adipose tissue was significantly higher in the high-dose BF group. Findings from this study suggest that in type 2 diabetes with insulin resistance, hypertriglyceridemia is closely linked to adiponectin.
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PMID:Short-term effect of bezafibrate on the expression of adiponectin mRNA in the adipose tissues: a study in spontaneously type 2 diabetic rats with visceral obesity. 1575 52

Adiponectin is a novel and important member of the adipocytokine family which has regulatory functions in the glucose and lipid metabolism. Adiponectin stimulates fatty acids oxidation, reduces plasma triglycerides, and improves glucose metabolism by increasing the insulin sensitivity. In addition, adiponectin inhibits the inflammatory process that accompanies atherogenesis, as it reduces the expression of endothelial adhesion molecules, macrophage-to-foam cell transformation, tumor necrosis factor-alpha (TNF-alpha) expression in macrophages and adipocytes, and smooth muscle cell proliferation. Several insulin-resistant states, such as obesity and type 2 diabetes, or cardiovascular diseases, have been found to be associated with low levels of plasma adiponectin. Thus, therapeutic approaches aimed at increasing the adiponectin concentrations or the adiponectin tissue sensitivity and action could represent a novel treatment strategy for insulin resistance in type 2 diabetes and might have therapeutic implications as an anti-obesity drug or as an anti-atherogenic plasma protein.
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PMID:[Adiponectin: a new link between obesity, insulin resistance and cardiovascular disease]. 1576 12

The Gly972Arg substitution of the insulin receptor substrate-1 (IRS-1) gene and the Pro12Pro genotype of the peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) gene have been suggested to be associated with type 2 diabetes mellitus. In this study, the influence of these two polymorphisms on serum adiponectin concentrations was investigated. The Pro12Ala polymorphism of the PPARgamma2 gene and the Gly972Arg polymorphism of the IRS-1 gene were genotyped in 252 young Finnish servicemen. The Ala12Ala genotype of PPARgamma2 was associated with a higher adiponectin level compared to the Pro12Ala genotype (p=0.02) and the Pro12Pro genotype (p=0.02). Total (p=0.02) and low-density lipoprotein (LDL) cholesterol (p=0.03) levels were higher in subjects with the Pro12Pro genotype compared to the Pro12Ala genotype. No difference was observed in serum adiponectin level between the IRS-1 genotype groups. The subjects with X972Arg of this gene had high total and LDL cholesterol levels (p<0.05). The interaction between the PPARgamma2 and IRS-1 genes with respect to their effects on adiponectin levels was statistically significant (p=0.02). Adiponectin was significantly higher (p<0.05) in subjects who simultaneously had the Ala/Ala (PPARgamma2)+Gly/Gly (IRS-1) genotype combination compared to subjects with the Pro/Pro+Gly/Gly and Pro/Ala+Gly/Gly genotype combinations. Total and LDL cholesterol was higher (p<0.05) in subjects with Pro/Pro+X/Arg compared to subjects with the two before mentioned genotype combinations. We conclude that the Ala12Ala genotype of PPARgamma2 is associated with elevated adiponectin level, and that the PPARgamma2 and IRS-1 genes have a possible interaction in their effects on adiponectin concentration.
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PMID:Common polymorphisms in the PPARgamma2 and IRS-1 genes and their interaction influence serum adiponectin concentration in young Finnish men. 1578 Nov 95

Adiponectin is the most abundant adipose-specific protein. Its expression is reduced in obesity, insulin resistance and type 2 diabetes, and plasma concentrations are inversely related to body weight, especially visceral adiposity. Adiponectin is also inversely associated with other traditional cardiovascular risk factors, such as blood pressure, low-density lipoprotein cholesterol and triglyceride levels, and is positively related to high-density lipoprotein cholesterol (HDL-C) levels. Recent research has indicated that adiponectin has anti-inflammatory, anti-atherogenic and antidiabetic properties. The ability of adiponectin to reduce insulin resistance in conjunction with its anti-inflammatory and anti-atherogenic properties makes this novel adipocytokine a promising therapeutic target, and agents that enhance adiponectin secretion or action have potential for treatment of metabolic and vascular disease. Current management strategies that may increase endogenous adiponectin production in humans include weight loss, soy protein and therapy with peroxisome proliferator-activating receptor gamma (PPARgamma) agonists.
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PMID:Adiponectin: Identification, physiology and clinical relevance in metabolic and vascular disease. 1582 91


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