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)

Peroxisome proliferator-activated receptor (PPAR)-gamma ligands are insulin sensitizers, widely used in the treatment of type 2 diabetes. A consistent observation in preclinical species is the development of cardiac hypertrophy after short-term treatment with these agents. The mechanisms for this hypertrophy are incompletely understood. Given the important role of insulin signaling in the regulation of myocardial size, we tested the hypothesis that augmentation of myocardial insulin signaling may play a role in PPAR-gamma ligand-induced cardiac hypertrophy. We treated mice with cardiomyocyte-restricted knockout of insulin receptors (CIRKO) and littermate controls (wild type) with 2-(2-(4-phenoxy-2-propylphenoxy) ethyl) indole-5-acetic acid (COOH), which is a non-thiazolidinedione PPAR-gamma agonist for 2 wk. Two weeks of COOH treatment increased heart weights by 22% in CIRKO mice and 16% in wild type, and induced similar fold increase in the expression of hypertrophic markers such as alpha-skeletal actin, brain natriuretic peptide, and atrial natriuretic peptide in CIRKO and wild-type (WT) hearts. COOH treatment increased plasma volume by 10% in COOH-treated WT and CIRKO mice but did not increase systolic or diastolic blood pressure. Echocardiographic analysis was also consistent with volume overload, as evidenced by increased left ventricular diastolic diameters and cardiac output in COOH-treated CIRKO and WT mice. These data indicate that cardiac hypertrophy after PPAR-gamma agonist treatment can occur in the absence of myocardial insulin signaling and is likely secondary to the hemodynamic consequences of plasma volume expansion.
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PMID:Cardiac hypertrophy caused by peroxisome proliferator- activated receptor-gamma agonist treatment occurs independently of changes in myocardial insulin signaling. 1782 61

Appropriate tools are necessary for predicting cardiovascular events in patients with diabetes mellitus because of their high incidence. In this study, we assessed whether a combination of brain natriuretic peptide (BNP) and C-reactive protein (CRP) measurement were useful prognosticators in patients with type 2 diabetes mellitus. One hundred and nine patients with type 2 diabetes mellitus, aged 52 to 93 years, were examined at outpatient clinics for blood, urinary samples, and echocardiography. They were then followed prospectively. During the average follow-up period of 30 months (range, 3 to 37), 15 patients (14%) had cardiovascular events: This was the first event in 5 patients and a recurrence in 10. Cox regression analysis showed that the past event (hazard ratio [HR] 4.819 [95% confidence interval (CI): 1.299-17.881]; p = 0.019) and plasma BNP level (HR 1.007 [95% CI: 1.002-1.012]; p = 0.010] were independently significant factors for the cardiovascular events during the follow-up period. Patients with plasma BNP > or =53 pg/mL and CRP > or =0.95 mg/dL demonstrated the highest incidence in cardiovascular event, compared to those categorized into either or both low levels of BNP and CRP. This study suggests that combination of plasma BNP and CRP measurement provides the additive prognostic information of cardiovascular events in patients with type 2 diabetes mellitus.
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PMID:Combined use of brain natriuretic peptide and C-reactive protein for predicting cardiovascular risk in outpatients with type 2 diabetes mellitus. 1796 72

Cardiovascular disease is the leading cause of death among patients with Type 2 diabetes mellitus. The main forms of structural heart disease associated with diabetes are coronary heart disease and diabetic cardiomyopathy, which is characterized by left ventricular hypertrophy, left ventricular diastolic and systolic dysfunction. Asymptomatic structural heart disease is common and associated with a poor prognosis in patients with diabetes. Contemporary practice guidelines do not recommend screening of asymptomatic individuals for structural heart disease. Potential screening modalities, such as echocardiography, are costly and inaccessible. A simple, inexpensive blood test for brain natriuretic peptide is a useful marker of structural heart disease and is a prime candidate for screening patients with Type 2 diabetes mellitus and prioritizing referral for echocardiography.
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PMID:Early detection and significance of structural cardiovascular abnormalities in patients with Type 2 diabetes mellitus. 1809 11

This study was aimed to compare the effect of insulin plus rosiglitazone with that of insulin plus metformin on the level of serum N-terminal pro-brain natriuretic peptide (NT-BNP) in patients with type 2 diabetes mellitus, and to find out whether serum NT-BNP can be used as an index for predicting heart failure induced by rosiglitazone in the cases of type 2 diabetes mellitus. Sixty type 2 diabetic patients were recruited and were randomly divided into two groups: group A (n = 30) received insulin plus rosiglitazone (4 mg/d) and group B (n = 30) received insulin plus metformin. The observations covered an 8-weeks' course of treatment. Serum NT-BNP was measured at the beginning and at the end of 8 weeks. The Before-After study revealed that the level of serum NT-BNP did not change apparently in the two groups (P >0.05). There was no remarkable difference in the level of serum NT-BNP between the two groups (P>0.05). There were 3 cases with edema in the group of insulin plus rosiglitazone, but none with heart failure; in these three cases, the mean serum NT-BNP level at the end of the treatment exhibited an increase of 108.99 fmol/ml when compared with that at the beginning. Neither insulin plus rosiglitazone nor insulin plus metformin had apparent effect on the level of serum NT-BNP in the patients with type 2 diabetes mellitus. The question of whether serum NT-BNP is a predictive index of heart failure awaits answers given by more observation on type 2 diabetes mellitus patients using rosiglitazone.
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PMID:[Effect of insulin plus rosiglitazone or metformin on serum N-terminal pro-brain natriuretic peptide in type 2 diabetes mellitus: a randomized-controlled study]. 1869 56

With the aim to investigate influence of glycemic control on clinical state and course of disease, renal function, and neurohormonal profile of patients with chronic heart failure (CHF) and type 2 diabetes mellitus (DM) we studied 81 patients with NYHA functional class (FC) II - III CHF, left ventricular ejection fraction (LVEF) 45% and type 2 DM. As a result of randomization 2 groups were formed - active with achievement of target levels of glycemia (n=41) and usual treatment (n=40). Retrospective analysis in dependence of efficacy of sugar lowering therapy was also conducted. Group 1 (n=18) comprised patients with achieved 1% lowering of glycated hemoglobin (HbA1 ), group 2 (n=26) - patients with bA1c lowering < 1%, group 3 (n=31) - patients with increase of HbA1 . Total duration of the investigation for the first analysis was 12, for the second - 6 months. Control examination was carried out at baseline, after 6 and 12 months of investigation and included assessment of clinico-functional status, glomerular filtration rate, neurohormonal profile (brain natriuretic peptide, noradrenalin, and angiotensin II). The state of carbohydrate metabolism was assessed with the help of determination of the level of HbA1c and oral glucose tolerance test. Absence of dynamics of glycemia in active and nonactive groups, in the active group improvement of clinico-functional status, quality of life, and parameters of remodeling was noted. Complementary retrospective analysis revealed improvement of functional status, renal function, and lowering of RAAS activity at 1% lowering of HbA1 and achievement of its target values. With this it was shown that betterment of functional possibilities ensued at lowering of HbA1c level not less than by 0.8%. Thus necessity and efficacy of strict glycemic control of DM in patients with CHF was proved.
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PMID:[Effect of strict glycemic control on clinical state and course of the disease in patients with chronic heart failure and type II diabetes mellitus. Results of the REMBO "rational effective multicomponent therapy in the struggle against diabetes mellitus in patients with congestive heart failure" study]. 1899 16

A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedigrees totalling 39 557 subjects of European origin. A meta-analysis of the seven case-control studies (n = 39 040) showed a nominal protective effect [odds ratio (OR) = 0.86 (0.79-0.94), P = 0.0006] of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (n = 49 279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D [OR = 0.86 (0.80-0.92), P = 1.4 x 10(-5)]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample sizes.
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PMID:The T-381C SNP in BNP gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49 279 subjects. 1937 85

A 3-year multicenter, prospective, randomized, open-label trial (ADVANCED-J) compared the effect of an increased dose of angiotensin-II receptor blocker (ARB) with that of a maintenance dose of ARB plus calcium channel blocker (amlodipine) on blood pressure (BP) control, nephropathy and atherosclerosis in patients with type 2 diabetes and hypertension in whom the usual ARB dose failed to control BP. A cross-sectional analysis using baseline data was conducted. Of 316 patients (recruited between September 2004 and December 2005), 228 patients were evaluated by multiple regression analysis using two models after randomization and exclusions. Model 1 assessed 13 baseline variables (age, sex, estimated diabetes duration, estimated hypertension duration, HbA1c, brain natriuretic peptide (BNP), high-sensitive C-reactive protein (hsCRP), triglycerides (TGs), total cholesterol (TCHO), diabetic retinopathy (DMR), systolic morning home BP (HBP), diastolic morning HBP and brachial-ankle pulse wave velocity (baPWV)) for correlation with the urinary albumin creatinine excretion rate (UACR). In model 2, systolic and diastolic morning HBP was replaced by systolic and diastolic office BP. The systolic morning HBP and systolic office BP or diastolic morning HBP and diastolic office BP correlations were weak, but significant (r=0.43 and 0.48, respectively). BNP, HbA1c, DMR and estimated diabetes duration were significantly correlated with UACR in both models 1 and 2. Although systolic office BP did not show a significant correlation with UACR in model 2, systolic morning HBP showed a significant correlation with UACR in model 1. Morning HBP, but not office BP, may be a significant marker of nephropathy in Japanese patients with type 2 diabetes.
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PMID:Morning home blood pressure may be a significant marker of nephropathy in Japanese patients with type 2 diabetes: ADVANCED-J study 1. 1955 3

Sleep-disordered breathing (SDB), especially sleep apnea-hypopnea syndrome, is often observed in patients with type 2 diabetes mellitus; but there are only a few studies on SDB in Japanese diabetic subjects. We investigated the prevalence of SDB in diabetic patients; associations between severity of sleep apnea (SA) and clinical factors, visceral fat, and adiponectin; and associations between type of SA and clinical factors. In the present study, 40 Japanese diabetic patients underwent overnight cardiorespiratory monitoring, and night and morning measurements of serum adiponectin concentrations. Sleep apnea was detected in Japanese diabetic patients at a high prevalence (77.5%). The following variables were associated with SDB: age, body mass index, estimated visceral fat area, and nocturnal reduction in serum adiponectin concentrations. The prevalence of central sleep apnea (CSA, >or=5/h) was 32.3% among diabetic SDB patients. Diabetic SDB patients with CSA had higher hemoglobin, increased intima-media thickness, and higher plasma brain natriuretic peptide levels than those without CSA (<5/h). In conclusion, our study demonstrated a high prevalence of SDB in Japanese diabetic patients, which correlated with visceral fat area and adiponectin. A high frequency of CSA was noted in diabetic SDB patients, together with high hemoglobin, high brain natriuretic peptide, and increased intima-media thickness. The present results of prevalence of SDB may be relevant to the higher incidence of cardiovascular disease in diabetic patients, which need to be clarified in future studies.
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PMID:Characteristics of sleep-disordered breathing in Japanese patients with type 2 diabetes mellitus. 1991 47

Peroxisome proliferator-activated receptor (PPAR)-gamma modulators, a class of antidiabetic drugs, have been associated with cardiovascular risks in type 2 diabetes in humans. The objective of this study was to explore possible cardiovascular risk biomarkers associated with PPAR-gamma in rodents that could provide an alert for risk to humans. Normal, myocardial infarction-induced heart failure (HF) or Zucker diabetic fatty (ZDF) rats were used. Rats (n = 5-6) were treated with either vehicle or rosiglitazone (RGZ; 3 or 45 mg/kg/day p.o.) for 4 weeks. Biomarkers for potential cardiovascular risks were assessed, including 1) ultrasound for cardiac structure and function; 2) neuroendocrine and hormonal plasma biomarkers of cardiovascular risk; 3) pharmacogenomic profiling of cardiac and renal tissue by targeted tissue low-density gene array representing ion channels and transporters, and components of the renin-angiotensin-aldosterone system; and 4) immunohistochemistry for cardiac fibrosis, hypertrophy, and inflammation (macrophages and tumor necrosis factor-alpha). HF was confirmed by increase in cardiac brain natriuretic peptide expression (p < 0.01) and echocardiography. Adequate exposure of RGZ was confirmed by pharmacokinetics (plasma drug levels) and the pharmacodynamic biomarker adiponectin. In normal or HF rats, RGZ had no negative effects on any of the biomarkers investigated. Similarly, RGZ had no significant effects on gene expression except for the increase in interleukin-6 mRNA expression in the heart and decrease in epithelial sodium channel beta in the kidney. In contrast, echocardiography showed improved cardiac structure and function after RGZ in ZDF rats. Taken together, this study suggests a limited predictive power of these preclinical models in respect to observed clinical adverse effects associated with RGZ.
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PMID:Pharmacogenomic, physiological, and biochemical investigations on safety and efficacy biomarkers associated with the peroxisome proliferator-activated receptor-gamma activator rosiglitazone in rodents: a translational medicine investigation. 2051 51

This study evaluated the relationship between natriuretic peptide levels and a wide range of echocardiography parameters in a population of thirty-three patients with poorly regulated type 2 diabetes, and no known heart failure. Natriuretic peptides brain natriuretic peptide (BNP) and N-terminal prohormone BNP (NT-proBNP) were measured. Transthoracic echocardiography was performed and cardiac volumes and ejection fraction were measured. Doppler and tissue Doppler were measured and diastolic function was stratified according to recent guidelines. Very few echocardiography parameters were correlated with BNP or NT-proBNP levels. However, left atrial end-systolic volume indexed for body surface area was correlated with natural logarithm (ln) BNP and ln NT-proBNP (r=0.62 and r=0.60; P<0.05). There were significant differences in ln BNP and ln NT-proBNP levels between those with normal and those with abnormal diastolic function (1.4 vs 3.1; P<0.001 and 3.4 vs 5.8; P<0.001). This study showed that very few echocardiography parameters were correlated with BNP or NT-proBNP levels in patients with poorly regulated type 2 diabetes, which in part contradicts previous studies in other diabetic populations. The exception was left atrial end-systolic volume that showed a moderate correlation with BNP or NT-proBNP levels. There were significant differences in BNP and NT-proBNP levels between the group with normal left ventricular diastolic function and the group with abnormal diastolic function.
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PMID:Relationship between natriuretic peptides and echocardiography parameters in patients with poorly regulated type 2 diabetes. 2053 39


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