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)

Phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins, and plays an essential role in HDL metabolism. The regulation of PLTP is poorly understood and recent evidence suggests that PLTP activity increases during acute-phase response. Since type 2 diabetes is associated with chronic subclinical inflammation, the objective is to determine whether inflammation modulates PLTP in diabetes. Plasma PLTP activity was assayed by measuring the transfer of radiolabeled phosphatidylcholine from liposomes to HDL and high-sensitivity C-reactive protein (CRP) by immunoturbidimetric assay in 280 type 2 diabetic patients and 105 controls. Plasma PLTP activity (2364+/-651 nmol/ml/h versus 1880+/-586 nmol/ml/h in control, mean +/- S.D., P <0.01) and CRP (1.64(0.89-3.23)mg/l versus 0.99(0.53-2.23 mg/l, median (interquartile range), P<0.01) were increased in diabetic subjects. PLTP activity correlated significantly with age, BMI, HbA1c, log(CRP) and apolipoprotein AI and B in diabetic subjects. General linear model analysis showed that only apolipoprotein AI, age, BMI, and log(CRP) were independent determinants of PLTP activity. In conclusion, PLTP activity is increased in diabetes and apolipoprotein AI is a major determinant of PLTP activity. There is also an independent association between CRP and PLTP activity, suggesting that subclinical inflammation may influence PLTP activity in diabetes.
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PMID:Plasma phospholipid transfer protein activity and subclinical inflammation in type 2 diabetes mellitus. 1575 64

Regular exercise offers protection against all-cause mortality, primarily by protection against cardiovascular disease and Type 2 diabetes mellitus. The latter disorders have been associated with chronic low-grade systemic inflammation reflected by a two- to threefold elevated level of several cytokines. Adipose tissue contributes to the production of TNF-alpha, which is reflected by elevated levels of soluble TNF-alpha receptors, IL-6, IL-1 receptor antagonist, and C-reactive protein. We suggest that TNF-alpha rather than IL-6 is the driver behind insulin resistance and dyslipidemia and that IL-6 is a marker of the metabolic syndrome, rather than a cause. During exercise, IL-6 is produced by muscle fibers via a TNF-independent pathway. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra and IL-10 and inhibits the production of the proinflammatory cytokine TNF-alpha. In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. We suggest that regular exercise induces suppression of TNF-alpha and thereby offers protection against TNF-alpha-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine that is produced and released by contracting skeletal muscle fibers, exerting its effects in other organs of the body. Here we suggest that myokines may be involved in mediating the health-beneficial effects of exercise and that these in particular are involved in the protection against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.
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PMID:The anti-inflammatory effect of exercise. 1577 55

We tested the hypothesis that elevated levels of plasma high-sensitivity C-reactive protein (HSCRP) are associated with insulin resistance/hyperinsulinemia and cardiovascular autonomic dysfunction in type 2 diabetic patients without insulin treatment. The study group consisted of 17 type 2 diabetic patients with high HSCRP (0.3-1.0 mg/dL; age, 59+/-8 years, mean+/-SD; high HSCRP group). The control group consisted of 18 age-matched type 2 diabetic patients with low HSCRP (<0.3 mg/dL; 59+/-7 years; low HSCRP group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentration, and cardiac metaiodobenzylguanidine (MIBG) labeled with iodine 123 scintigraphic findings. Baroreflex sensitivity was lower in the high HSCRP group than in the low HSCRP group (P<.05). Early and delayed 123I-MIBG myocardial uptake values were lower (P<.05 and P<.005, respectively) and the percent washout rate of 123I-MIBG was higher (P<.01) in the high HSCRP group than in the low HSCRP group. Fasting plasma insulin concentration (P<.01) and the homeostasis model assessment index (P<.01) were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis revealed that the level of HSCRP was independently predicted by fasting plasma insulin concentration and myocardial uptake of 123I-MIBG at a delayed phase. Our results suggest that high levels of HSCRP are associated with depressed cardiovascular autonomic function and hyperinsulinemia and that fasting plasma insulin concentration and myocardial uptake of 123I-MIBG at a delayed phase are independent predictors of HSCRP level in our Japanese patients with type 2 diabetes mellitus.
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PMID:High-sensitivity C-reactive protein is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients. 1579 66

Endothelial dysfunction increases risk for type 2 diabetes. We examined whether variation in the gene for E-selectin (SELE), a biomarker of endothelial dysfunction, was associated with levels of E-selectin or diabetes quantitative traits (including fasting levels of insulin and hemoglobin A(1c)) in 719 nondiabetic participants of the Nurses' Health Study or with risk of diabetes in 602 incident (over 10 years of follow-up) cases and 655 control women matched for age, race, and fasting status. Variation in three single nucleotide polymorphisms previously associated with cardiovascular disease risk and having effects on E-selectin function, S128R, G98T, and L554F, was not significantly (p > 0.05) associated with levels of E-selectin or diabetes quantitative traits, or with risk of incident diabetes in the primary analysis. Among women with low levels of subclinical inflammation (C-reactive protein levels below the population median), S128R R allele carriers had a diabetes risk factor-adjusted relative risk of incident diabetes of 1.71 (95% confidence interval, 1.04 to 2.81) relative to those with the SS genotype. Apart from an association in this subgroup, we conclude that the E-selectin variants we examined are not important genetic risk factors for type 2 diabetes in women.
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PMID:E-selectin genotypes and risk of type 2 diabetes in women. 1628 35

The increased number of oral agents available to treat patients with type 2 diabetes mellitus (DM) has presented clinicians with choices about how to combine them when monotherapy is not adequate to achieve glycemic targets. Initial studies focused on whether a combination of 2 active drugs was better than a single active agent plus placebo. Several factors need to be considered before results of combination regimens from a given protocol can be compared with results from a different study regimen. Some of these factors include population characteristics, baseline control and prior therapies, length of study, and outcomes (glycemic and nonglycemic). Additional factors to be considered are costs and side effects. These studies generally demonstrate that combination therapy is more likely than monotherapy to achieve glucose control in patients not at glycemic targets. The data also demonstrate that inadequate glucose control with a given medication does not necessarily indicate drug failure; indeed, adding a new agent to an existing regimen is typically better than using the new agent as monotherapy. More recent studies have begun to compare regimens each containing 2 drugs (usually with 1 medication in common). Outcomes beyond glycemic control have been measured, including traditional (e.g., lipid profiles, albuminuria) and nontraditional (e.g., high-sensitivity C-reactive protein, plasminogen activator inhibitor type-1) markers. However, modifying traditional markers with these medications has not yet been shown to improve outcomes; modifying nontraditional markers is even less certain. None of these trials have been extended long enough to report on hard clinical end points. Nonetheless, certain combinations may end up being preferable because they have better impact on nonglycemic end points while maintaining equivalent degrees of glucose control. Finally, the costs of multiple medications for DM need to be weighed in the decision-making process faced by clinicians.
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PMID:How to select and combine oral agents for patients with type 2 diabetes mellitus. 1585 May 48

Several studies suggest that inflammation plays an important role in the pathogenesis of diabetes mellitus, as well as atherosclerosis, and acute-phase reactants have been proposed as monitors for the ongoing process of these diseases. We studied the clinical significance of serum high-sensitivity C-reactive protein (hs-CRP) in relation to chronic diabetic complications using 114 Japanese patients with Type 2 diabetes mellitus. The hs-CRP values were normalized by logarithmic transformation for statistical analysis. Retinopathy and hypertension were extracted as significant modulators for the hs-CRP value in the diabetic patients, in addition to previously known factors, age, and body mass index (BMI), by multivariate analysis. The hs-CRP level in normotensive diabetic patients without retinopathy was not significantly different from that of normal control participants after adjustment for age and BMI. The hs-CRP value was significantly high in the patients with hypertension, despite the existence or absence of diabetes. On the other hand, the hs-CRP level of the diabetic patients complicated with retinopathy was low especially in those with hypertension. The frequency of patients having an hs-CRP value above 1.0 mg/l who are thought to be at risk for cardiovascular diseases was also high in the patients complicated with hypertension and low in the diabetic patients with retinopathy. These results indicate that the presence or absence of hypertension and retinopathy should be taken into consideration for the interpretation of the serum hs-CRP in diabetic patients.
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PMID:Retinopathy and hypertension affect serum high-sensitivity C-reactive protein levels in Type 2 diabetic patients. 1586 55

Rosiglitazone, an agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma ), is an insulin-sensitizing antidiabetic agent and inhibits restenosis in animal blood vessels. However, its benefit for patients with type 2 diabetes and coronary artery disease (CAD) after percutaneous coronary intervention is unknown. Patients with diabetes and CAD who had undergone percutaneous coronary intervention were randomized to either receive or not receive rosiglitazone (4 mg/d) for 6 months. After 6 months of rosiglitazone treatment, the plasma levels of fasting glucose and insulin and those of hemoglobin A1C and homeostasis model assessment of insulin resistance were significantly decreased in the rosiglitazone group as compared with baseline levels and those in the control group. After 2 and 6 months of rosiglitazone treatment, the plasma level of high-density lipoprotein was significantly increased in the rosiglitazone group. In addition, plasma levels of monocyte chemoattractant protein-1 and C-reactive protein and hyperresponsiveness of low-dose lipopolysaccharide-induced monocyte chemoattractant protein-1 secretion from monocytes were reduced. Furthermore, the occurrence of coronary events was significantly decreased in the rosiglitazone group at 6-month follow-up. Our data indicate that rosiglitazone may protect the vascular wall through not only improving the features of metabolic disorders but also reducing proinflammatory responses and the occurrence of coronary events in patients with diabetes and CAD after percutaneous coronary intervention.
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PMID:Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces clinical inflammatory responses in type 2 diabetes with coronary artery disease after coronary angioplasty. 1587 88

The present review considers the background to terminology that relates foods, glycaemia and health, including 'available carbohydrate', 'glycaemic index' (GI), 'glycaemic glucose equivalent', 'glycaemic response index' and 'net carbohydrate', and concludes that central to each of these terms is 'glycaemic load' (GL). GL represents the acute increase in exposure of tissue to glucose determined by foods; it is expressed in ingested glucose equivalents (per 100 g fresh weight or per serving), and is regarded as independent of the state of glucose metabolism from normal to type 2 diabetes mellitus (T2DM). Ad libitum studies in overweight or obese adults and children show that low-GL diets are associated with marked weight benefits, loss of adiposity and reduced food intake. Weight benefits appear on low-glycaemic v. high-glycaemic available carbohydrates, unavailable v. available carbohydrates and protein v. available carbohydrate. Energy intake immediately after lowering of meal GL via carbohydrate exchanges is apparent only after a threshold cumulative intake of >2000 MJ. Various epidemiological and interventional studies are discussed. A relationship between GL and the development of T2DM and CHD is evident. Studies that at first seem conflicting are actually consistent when data are overlaid, such that diets with a GL of >120 glucose equivalents/d would appear to be inadvisable. Whereas certain studies might place GI as being slightly stronger than GL in relation to T2DM risk, this situation appears to be associated with observations in a lower range of GL or when the range of GI is too narrow for accuracy; nevertheless, authors emphasise the importance of GL. Among the studies reviewed, GL offers a better or stronger explanation than GI in various observations including body weight, T2DM in nurses, CHD, plasma triacylglycerols, HDL-cholesterol, high-sensitivity C-reactive protein and protein glycation. Where information is available, the associations between risk factors and GL are either similar or stronger in the overweight or obese, as judged by BMI, and apply to both body weight and blood risk factors. The implications tend to favour a long-term benefit of reducing GL, for which further study is necessary to eliminate any possibility of publication bias and to establish results in clinical trials with overweight and obese patients.
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PMID:Low-glycaemic diets and health: implications for obesity. 1587 29

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each 2-month treatment period. Ramipril alone or combined therapy significantly reduced blood pressure when compared with simvastatin alone. When compared with ramipril alone, simvastatin alone or combined therapy significantly improved the lipoprotein profile. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and reduced plasma levels of malondialdehyde relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy when compared with simvastatin or ramipril alone (P<0.001 by ANOVA). When compared with simvastatin or ramipril alone, combined therapy significantly reduced high-sensitivity C-reactive protein levels (P=0.004 by ANOVA). Interestingly, combined therapy or ramipril alone significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P<0.015 by ANOVA). Ramipril combined with simvastatin had beneficial vascular and metabolic effects when compared with monotherapy in patients with type 2 diabetes.
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PMID:Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. 1588 29

Patients with type 2 diabetes mellitus have a greater risk of cardiovascular disease than nondiabetic individuals. These patients are often insulin resistant and have an associated clustering of risk factors that contribute to cardiovascular disease. The risk factors include dyslipidemia, hypertension, altered hemostasis, and chronic inflammation. A primary objective in the management of type 2 diabetes mellitus is normalization of blood glucose levels; however, some of the oral drugs used to control blood glucose levels have significant effects on these risk factors. In this article, we review the current data involving the modification of these cardiovascular risk factors by the biguanide (metformin), the thiazolidinediones (troglitazone, rosiglitazone, and pioglitazone), the alpha-glucosidase inhibitors (miglitol, acarbose), and the insulin secretagogs (glyburide [glibenclamide], glipizide, chlorpropamide, tolbutamide, tolazamide, glimepiride, repaglinide, and nateglinide). Generally, the thiazolidinediones improve hemostasis and endothelial function and reduce blood pressure, while having variable effects on dyslipidemia. Metformin improves dyslipidemia and altered hemostasis and decreases plasma C-reactive protein levels with little or no effect on blood pressure. Data on the effects of the alpha-glucosidase inhibitors and insulin secretagogs are sparse; however, these drugs appear to have little or no effect on cardiovascular risk factors.
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PMID:Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents. 1590 Dec 7


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