Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin is a serum protein secreted by adipocytes and accounts for approximately 0.01% of total plasma protein. In healthy patient populations adiponectin can be found in concentrations of 7-12 mg/l. Unlike other adipocyte products, adiponectin correlates with decreased free fatty acid blood concentrations and reduced body mass index or body weight. Adiponectin protects from vascular diseases by inhibiting local proinflammatory signals, preventing preatherogenic plaque formation, and by impeding arterial wall thickening. Proinflammatory state and endothelial dysfunction are nominators of the metabolic syndrome, a complex set of risk factors including vascular and metabolic insulin resistance with hyperglycemia, hypertension, and dyslipidemia. Over the past years, thiazolidinediones, like rosiglitazone or pioglitazone, became known as a therapeutic option for patients suffering from the metabolic syndrome. It is considered that insulin sensitizers exert their benefit through indirect induction of adiponectin expression. Clinical studies have confirmed that treatment with thiazolidinediones may increase adiponectin concentrations in patients with type 2 diabetes independent from improvements in blood glucose control or parallel treatment with insulinotropic drugs. These findings suggest that adiponectin may have a diagnostic value and can be used especially for monitoring treatment success. This review summarizes recent biological and clinical data indicating that adiponectin may be the molecular link between obesity and insulin resistance and may serve as a biomarker for the metabolic syndrome.
 ...
PMID:Biological background and role of adiponectin as marker for insulin resistance and cardiovascular risk. 1628 70

This study was done to see whether 27-base pair repeats polymorphism in intron 4 of ecNOS gene is associated with carotid atherosclerosis in type 2 diabetic patients. The polymorphism was identified by polymerase chain reaction (PCR). Ultrasound parameters of carotid atherosclerosis were analyzed in relation to the genotype in 210 patients with type 2 diabetes. The ecNOS4a allele was detected in 34 (16.2%) of this study group. With the exception of the plaque count (P = 0.069), all other parameters obtained by ultrasound examination of carotid arteries were significantly correlated with presence of ecNOS4a allele (P < 0.05). As all the measured carotid parameters correlated well each other, we selected the total mean carotid IMT (intima-media thickness) value to be used for this analysis. In the multivariate analysis including several variables such as age, sex, hypertension, LDL cholesterol, waist-hip ratio, and fasting insulin, all determined to be significant by univariate analysis, ecNOS4a allele had a significant correlation with total mean IMT (P < 0.001). In conclusion, the ecNOS4a allele is associated with carotid atherosclerosis in type 2 diabetic patients in Korea.
 ...
PMID:Association of the endothelial nitric oxide synthase (ecNOS) gene polymorphism with carotid atherosclerosis in type 2 diabetes. 1637 20

Atherosclerosis is a long-term chronic inflammatory disease associated with increased concentrations of inflammatory hepatic markers, such as CRP and fibrinogen, and of peripheral origin, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. Peroxisome proliferator-activated receptor (PPAR-)-alpha is a ligand-activated transcription factor that regulates expression of key genes involved in lipid homeostasis and modulates the inflammatory response both in the vascular wall and the liver. PPAR-alpha is activated by natural ligands, such as fatty acids, as well as the lipid-lowering fibrates. PPAR-alpha agonists impact on different steps of atherogenesis: (1) early markers of atherosclerosis, such as vascular wall reactivity, are improved, (2) however, reduced expression of adhesion molecules on the surface of endothelial cells, accompanied by decreased levels of inflammatory cytokines, such as TNF-alpha, IL-1, and IL-6, leads to a decreased leukocyte recruitment into the arterial wall; (3) in later stages of the atherosclerotic process, PPAR-alpha agonists may promote plaque stabilization and reduce cardiovascular events, via effects on metalloproteinases, such as MMP9. Moreover, PPAR-alpha activation by fibrates also impairs proinflammatory cytokine-signaling pathways in the liver resulting in the modulation of the acute phase response reaction via mechanisms independent of changes in lipoprotein levels. Effective coronary artery disease (CAD) prevention requires the use of agents that act beyond low-density lipoprotein cholesterol-lowering. PPAR-alpha agonists appear to comprehensively address some of the abnormalities of the most common clinical phenotypes of the high CAD risk patient of the 21st century such as in the metabolic syndrome and type 2 diabetes: low high-density lipoprotein cholesterol, high triglycerides, small, dense low-density lipoprotein, and a proinflammatory, procoagulant state.
 ...
PMID:Modulation of hepatic inflammatory risk markers of cardiovascular diseases by PPAR-alpha activators: clinical and experimental evidence. 1642 52

Type 2 diabetes mellitus and obesity are the most common nutritional disorders in developed and developing countries. Increased prevalence of periodontal disease is a well-known complication of type 2 diabetes mellitus (DM). As obesity is generally the first step toward type 2 diabetes mellitus, it is possible to find exacerbated periodontal disease in obese patients, also. The purpose of this cross-sectional study was to investigate the periodontal status and aspartate aminotransferase and lactate dehydrogenase enzyme activities in gingival crevicular fluid (GCF) of type 2 diabetic and/or obese chronic periodontitis patients. A total of 39 chronic periodontitis patients participated in the study. The study population was divided into four groups according to body mass index and type 2 DM status: 1) type 2 DM obese patients, n = 8; 2) type 2 DM patients, n = 12; 3) obese patients, n = 8; 4) systemically healthy control group, n = 11. Enzyme activities in gingival crevicular fluid and periodontal status were evaluated. No significant differences in age, gingival index, plaque index, aspartate aminotransferase and lactate dehydrogenase enzyme activities were observed, but probing depths were significantly higher in the DM groups than in the control group. Obesity did not seem to be a significant factor in any parameters evaluated. The present study showed increased probing depth values for the diabetic groups but failed to show any significant relation between obesity and enzyme activity or periodontal status. However, the slightly increased probing depth values in the obese groups might be a clue to an impaired immune response and predisposition to periodontitis in that patient group.
 ...
PMID:Periodontal status and cytoplasmic enzyme activities in gingival crevicular fluid of type 2 diabetic and/or obese patients with chronic periodontitis. 1645 82

Thiazolidinediones, synthetic ligands for the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) receptor, are insulin-sensitizing drugs licensed for use in selected patients with type 2 diabetes mellitus. The potential therapeutic applications of the thiazolidinediones extend to other clinical specialties such as dermatology. Rosiglitazone and pioglitazone are being evaluated for the treatment of psoriasis. Type 2 diabetes and psoriasis may coexist prompting speculation that dual benefits might accrue for patients with both conditions. A recent open pilot study suggests that oral pioglitazone may be beneficial for moderate chronic plaque psoriasis. However, changes in antidiabetic medication must be made in the knowledge of the cautions and contraindications to oral agents as well as the impact on metabolic control. Further studies are required before the use of thiazolidinediones for psoriasis can be advocated.
 ...
PMID:Type 2 diabetes, psoriasis and thiazolidinediones. 1649 55

Individuals with type 2 diabetes are at increased risk of cardiovascular disease (CVD) mortality and display increased levels of subclinical CVD. Genetic variation in PTPN1, a diabetes susceptibility gene, was investigated for a role in diabetic atherosclerosis. The PTPN1 gene encodes protein tyrosine phosphatase-1B, which is ubiquitously expressed and plays a role in the regulation of several signaling pathways. Subclinical atherosclerosis was assessed in 590 Caucasian participants with type 2 diabetes in the Diabetes Heart Study using B-mode ultrasound measurement of carotid intima-media thickness (IMT) and computed tomography measurement of carotid calcified plaque (CarCP) and coronary calcified plaque (CorCP). Twenty-three single nucleotide polymorphisms (SNPs) in PTPN1 were genotyped and assessed for association with IMT, CarCP, and CorCP. A total of 12 SNPs within a block of linkage disequilibrium encompassing the coding sequence of PTPN1 were significantly associated with CorCP (P values from <0.0001 to 0.043) and 3 SNPs also within the block approached significance (P values from 0.058 to 0.066). In addition, a nine-SNP haplotype (GACTTCAGO) was also associated with increased CorCP under a dominant model (P = 0.01). No association was detected with IMT or CarCP. The associated SNPs and haplotype are the same as those observed to be associated with type 2 diabetes, insulin resistance, and fasting glucose in previous studies. With the inclusion of the most likely haplo-genotype for each individual, the heritability estimate of CorCP increased from 0.53 +/- 0.1 to 0.57 +/- 0.1 (P = 8.1 x 10(-10)), suggesting a modest but detectable effect of this gene on the phenotype of CorCP in type 2 diabetic patients.
 ...
PMID:Association of protein tyrosine phosphatase-N1 polymorphisms with coronary calcified plaque in the Diabetes Heart Study. 1650 27

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
 ...
PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in type 2 diabetes, but the relationship between CVD and type 2 diabetes is not well understood. The Diabetes Heart Study is a study of type 2 diabetes-enriched families extensively phenotyped for measures of CVD, type 2 diabetes, and metabolic syndrome. A total of 977 Caucasian subjects from 358 pedigrees (575 type 2 diabetic relative pairs) with at least two individuals with type 2 diabetes and, where possible, unaffected siblings were included in a genome scan. Qualitative traits evaluated in this analysis are with or without the presence of coronary calcified plaque (CCP) and with or without carotid calcified plaque (CarCP) measured by electrocardiogram-gated helical computed tomography. In addition, prevalent CVD was measured using two definitions: CVD1, based on self-reported history of clinical CVD (393 subjects), and CVD2, defined as CVD1 and/or CCP >400 (606 subjects). These discrete traits (type 2 diabetes, metabolic syndrome, CVD1, CVD2, CCP, and CarCP) frequently coincide in the same individuals with concordance ranging from 42.9 to 99%. Multipoint nonparametric linkage analysis revealed evidence for coincident mapping of each trait (type 2 diabetes, metabolic syndrome, CVD1, CVD2, CCP, and CarCP) to three different genomic regions: a broad region on chromosome 3 (70-160 cM; logarithm of odds [LOD] scores ranging between 1.15 and 2.71), chromosome 4q31 (peak LOD 146 cM; LOD scores ranging between 0.90 and 2.41), and on chromosome 14p (peak LOD 23 cM; LOD scores ranging between 1.43 and 2.31). Ordered subset analysis (OSA) suggests that the linked chromosome 3 region consists of at least two separate loci on 3p and 3q. In addition, OSA based on lipid measures and other traits identify family subsets with significantly stronger evidence of linkage (e.g., CVD2 on chromosome 3 at 87 cM subsetting on low HDL with an initial LOD of 2.19 is maximized to an LOD of 7.04 in a subset of 25% of the families and CVD2 on chromosome 14 at 22 cM subsetting on high triglycerides with an initial LOD of 1.99 maximized to an LOD of 4.90 in 44% of the families). When subjects are defined as affected by the presence of each trait (type 2 diabetes, metabolic syndrome, CVD1, and CCP), significant evidence for linkage to the 3p locus is observed with a peak LOD of 4.13 at 87 cM. While the correlated nature of the traits makes it unclear whether these loci represent distinct type 2 diabetes, metabolic syndrome, or CVD loci or single loci with pleiotropic effects, the coincident linkage suggests that identification of the underlying genes may help clarify the relationship of diabetes, metabolic syndrome, and CVD.
 ...
PMID:Coincident linkage of type 2 diabetes, metabolic syndrome, and measures of cardiovascular disease in a genome scan of the diabetes heart study. 1680 67

The objective of the study was to determine the most accurate metabolic syndrome (MS) definition among the definitions proposed by the International Diabetes Federation (IDF), the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATPIII]), and the World Health Organization (WHO) and to evaluate the cutoff point of waist circumference using the IDF definition for optimally defining MS in the Chinese population. One thousand thirty-nine Chinese patients older than 30 years and diagnosed with type 2 diabetes mellitus were investigated by randomized cluster sampling in the Shanghai downtown, and 1008 patients were analyzed in this study. Body mass measurements, resting blood pressure, fasting blood measures, and carotid atherosclerotic measurements including common carotid artery intima-media thickness (IMT) and carotid plaque were investigated. The IDF definition was compared with the other 2 definitions, and the carotid atherosclerosis was evaluated among the patients according to these definitions. (1) The MS prevalence was 50.0%, 55.7%, and 70.0% under the IDF, ATPIII, and WHO definitions, respectively. (2) The percentage of all the participants categorized as either having or not having the MS was 69.9% (under the IDF and ATPIII definitions) and 70.2% (under the IDF and WHO definitions). (3) Common carotid artery IMT of patients with MS determined by the IDF definition was thicker than those determined by the WHO and ATPIII definitions, and the percentage of carotid plaque of patients with MS determined by the IDF definition was greater than those determined by the WHO and ATPIII definitions. (4) When the cutoff point of waist circumference in men determined by the IDF definition was modified from 90 to 85 cm, common carotid artery IMT of the emerging male patients with MS was thicker than that of the male patients with MS determined by the original IDF definition. In conclusion, the prevalence of MS was 50.0%, 55.7%, and 70.0% under the IDF, ATPIII, and WHO definitions, respectively. The preferable IDF definition served as a better predictor of cardiovascular disease risk in the Chinese patients diagnosed with type 2 diabetes mellitus compared with the ATPIII and WHO definitions. The modified cutoff point of waist circumference in men under the IDF definition specific for the Chinese population (from 90 to 85 cm) might be more suitable for predicting atherosclerosis.
 ...
PMID:An evaluation of the International Diabetes Federation definition of metabolic syndrome in Chinese patients older than 30 years and diagnosed with type 2 diabetes mellitus. 1683 46

Connective tissue growth factor (CTGF) is expressed in atherosclerotic plaques. It is generally recognized that CTGF contributes to atherosclerosis by stimulating vascular smooth muscle cell (VSMC) proliferation and extracellular matrix production during the development of atherosclerosis. Recent studies indicate that CTGF may also contribute to plaque destabilization as it induces apoptosis and stimulates MMP-2 expression in VSMCs. Thiazolidinediones (TZDs), a new class of insulin sensitizing drugs for type 2 diabetes, inhibit atherosclerosis. However, their effect on CTGF expression in atherosclerotic plaques remains unknown. In this study, male LDL receptor-deficient mice were fed high-fat diet for 4 months to induce the formation of atherosclerotic plaques and then given the high-fat diet with or without pioglitazone for the next 3 months. At the end of the 7-month study, CTGF expression in aortic atherosclerotic lesions was examined. Results showed that CTGF expression was increased in mice fed the high-fat diet by seven-fold as compared to that in mice fed normal chow, but the treatment with pioglitazone significantly inhibited the high-fat diet-induced CTGF expression. To verify these in vivo observations, in vitro studies using human aortic SMC were conducted. Quantitative real-time PCR and Western blot showed that pioglitazone inhibited TGF-beta-stimulated CTGF expression. In conclusion, the present study has demonstrated that pioglitazone inhibits CTGF expression in mouse advanced atherosclerotic plaques and in cultured human SMCs, and hence unveiled a possible mechanism potentially involved in the inhibition of atherosclerosis by TZD.
 ...
PMID:Pioglitazone inhibits connective tissue growth factor expression in advanced atherosclerotic plaques in low-density lipoprotein receptor-deficient mice. 1690 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>