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)

Cytokines play an important role in the pathology associated with chronic inflammatory diseases. One of these cytokines, interleukin 6 (IL-6) is a major mediator of the host response to tissue injury, infection and bone resorption. In the present study, gingival crevicular fluid (GCF) level of IL-6 was determined in patients with non-insulin dependent diabetes mellitus (NIDDM) with periodontitis, adult periodontitis, and healthy controls by use of an enzyme linked immunosorbent assay (ELISA). Twenty-four NIDDM patients with periodontitis, twenty-four adult periodontitis and twenty-four healthy controls were selected for the study. GCF sampling was performed on the vestibular aspects of maxillary incisors and canine teeth. Plaque index (PI), gingival index (GI), gingival bleeding time index (GBTI), probing depth (PD) and probing attachment levels (PAL) were recorded from each sampling area and also the entire dentition. NIDDM and adult periodontitis patients had numerous sites with radiographic evidence of alveolar bone resorption, loss of attachment and pocket depth greater than 3 mm. The mean GCF IL-6 level was 2.43 +/- 0.97 ng/ml in NIDDM patients, 1.31 +/- 0.92 ng/ml in adult periodontitis and 0.62 +/- 0.58 ng/ml in healthy subjects, respectively (p < 0.05). GCF IL-6 levels were markedly higher in NIDDM and adult periodontitis groups compared to the healthy controls. No correlation was found between GCF IL-6 levels and all clinical parameters. These findings suggested that GCF IL-6 levels were significantly higher in the area of inflammation and periodontal destruction locally. The high IL-6 levels in NIDDM patients might be due to different microbial flora in periodontal pockets and altered immune system. Future studies are needed to evaluate the complex interaction among IL-6 GCF levels, host response and local microbial environment in the NIDDM patients.
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PMID:IL-6 levels in gingival crevicular fluid (GCF) from patients with non-insulin dependent diabetes mellitus (NIDDM), adult periodontitis and healthy subjects. 1069 91

The aim of this study was to investigate the potential role of adipose cytokines in the obesity-associated insulin resistance. To that end, we compared: 1) serum concentrations of interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), and leptin in eight healthy lean control females and in android obese female without (n = 14) and with (n = 7) type 2 diabetes; and 2) the levels of these cytokines both in serum and in sc adipose tissue in the 14 obese nondiabetic women before and after 3 weeks of a very low-calorie diet (VLCD). As compared with lean controls, obese nondiabetic and diabetic patients were more insulin resistant and presented increased values for leptin, IL-6, TNFalpha, and C-reactive protein. In the whole group, IL-6 values were more closely related to the parameters evaluating insulin resistance than leptin or TNFalpha values. VLCD resulted in weight loss and decreased body fat mass (approximately 3 kg). Insulin sensitivity was improved with no significant change in both serum and adipose tissue TNFalpha levels. In contrast, VLCD induced significant decreases in IL-6 and leptin levels in both adipose tissue and serum. These results suggest that, as for leptin, circulating IL-6 concentrations reflect, at least in part, adipose tissue production. The reduced production and serum concentrations after weight loss could play a role in the improved sensitivity to insulin observed in these patients.
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PMID:Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. 1099 30

Obesity is a major risk factor for insulin resistance and type 2 diabetes mellitus. Adipocytes secrete numerous substances that might contribute to peripheral insulin sensitivity. These include leptin, tumor necrosis factor alpha, Acrp30/adiponectin/adipoQ and interleukin 6, the potential roles of which are briefly reviewed here. Thiazolidinedione (TZD) antidiabetic drugs regulate gene transcription by binding to peroxisome proliferator activated receptor gamma, a nuclear hormone receptor found at its highest levels in adipocytes. A search for genes that are downregulated by TZDs in mouse adipocytes led to the discovery of an adipose-specific secreted protein called resistin. Resistin circulates in the mouse, with increased levels in obesity, and has effects on glucose homeostasis that oppose those of insulin. Thus, resistin is a potential link between TZDs, obesity and insulin resistance in the mouse. Future studies must address the mechanism of action and biological role of resistin and related family members in mice and humans.
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PMID:Resistin and obesity-associated insulin resistance. 1175 Aug 58

The assessment of markers of systemic inflammation, such as C-reactive protein (CRP) and interleukin 6 (IL6), could be used to identify persons at high risk of coronary heart disease (CHD). This study evaluates the relationship of CRP and IL6 with CHD risk factors in patients with type 2 diabetes mellitus (DM) with CHD and age and sex matched type 2 DM controls without CHD. CRP, IL-6, total plasma homocysteine (tHcy), lipoprotein (a) [Lp(a)] and sialic acid (SA) were determined in 55 type 2 diabetic patients with CHD and 51 age- and sex-matched type 2 diabetic controls without CHD. Multivariate and logistic regression analyses were used to relate these markers with CHD risk factors. CRP (P=0.02) and tHcy (P=0.03) were significantly higher in patients with CHD compared with the control group even after correction for age and sex. IL6, Lp(a), SA and lipid parameters were not significantly different between the two groups of patients. After adjustment for potential confounders, the odds ratio (OR) for elevated CRP was 2.00 (95% confidence interval [CI], 1.12-3.58) (P=0.02) but the OR for IL6 was 3.41 95% CI, 0.70-17.17 (P=0.14). Partial correlation analyses of CRP and IL6 with other variables showed significant correlation of CRP with tHcy, and SA in patients with CHD only. Our results support the inclusion of CRP (high-sensitivity assay), in the risk assessment of diabetic subjects.
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PMID:Association of C-reactive protein with coronary heart disease risk factors in patients with type 2 diabetes mellitus. 1216 Oct 55

Type 2 diabetes and obesity are major risk factors for the development of coronary artery disease (CAD) and premature atherosclerosis. Both conditions are associated with insulin resistance, oxidative stress, and inflammation. Inflammatory mediators, including plasma interleukin 6, tumor necrosis factor alpha, and tumor necrosis factor R are elevated in these individuals. The elevations of inflammatory mediators may contribute to the pathogenesis of atherosclerosis, because atherosclerosis is an inflammation of the arterial wall. There is evidence that the thiazolidinedione (TZD) class of drugs may alleviate some of the adverse atherosclerotic effects common in patients with type 2 diabetes. Considerable recent data suggest that the TZDs possess anti-inflammatory properties and exert an effect on the atherogenic process, including effects on endothelial function, monocyte/macrophage function, lipid abnormalities, smooth muscle cell migration, and fibrinolysis, all functions that are abnormal in the presence of insulin resistance. These actions of TZDs are consistent with the recently described anti-inflammatory effects of insulin. The use of TZDs as potent anti-inflammatory agents in patients with type 2 diabetes is an approach that would normalize glucose levels, as well as potentially alleviate the long-term risk of atherosclerosis.
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PMID:A rational approach to pathogenesis and treatment of type 2 diabetes mellitus, insulin resistance, inflammation, and atherosclerosis. 1223 Oct 76

The major risk factor for the development of insulin resistance and type 2 diabetes is obesity. A key role is the new understanding of adipocytes as an endocrine system. Adipocytes secrete numerous substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and interleukin 6. There is also a role of free fatty acids by blocking directly intracellular metabolism of glucose and by their lipotoxicity. The pre-receptor metabolism of cortisol may be enhanced in visceral adipose tissue by activation of 11 beta-hydroxysteroid dehydrogenase type 1. The new class of thiazolidinediones (glitazones), binding to the peroxisome proliferator activated receptor (PPAR-gamma) lowers the levels of resistin and increases adiponectin, resulting in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance should be an attempt to reduce body weight and to increase physical activity. These are successful means to avoid the development of type 2 diabetes from prediabetic states, as shown recently in 3 independent intervention trials.
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PMID:[From obesity to diabetes]. 1223 30

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.
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PMID:Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. 1282 59

In previous publications, we presented the hypothesis that repeated episodes of acute or chronic psychological stress could induce an acute phase response (APR) and subsequently a chronic inflammatory process such as atherosclerosis. In this paper, that hypothesis, namely that such stress can induce an APR and inflammation, has been extended to include a chronic inflammatory process(s), characterized by the presence of certain cytokines and acute phase reactants (APR), which is associated with certain metabolic diseases. The loci of origin of these cytokines, particularly interleukin 6 (IL-6), and their induction, has been considered. Evidence is presented that the liver, the endothelium, and fat cell depots are the primary sources of cytokines, particularly IL-6, and that IL-6 and the acute phase protein (APP), C-reactive protein (CRP), are strongly associated with, and likely play a dominant role in, the development of this inflammatory process which leads to insulin resistance, non-insulin dependent diabetes mellitus type II, and Metabolic syndrome X. The possible role of psychological stress and the major stress-related hormones as etiologic factors in the pathogenesis of these metabolic diseases, as well as atherosclerosis, is discussed. The fact that stress can activate an APR, which is part of the innate immune inflammatory response, is evidence that the inflammatory response is contained within the stress response or that stress can induce an inflammatory response. The evidence that the stress, inflammatory, and immune systems all evolved from a single cell, the phagocyte, is further evidence for their intimate relationship which almost certainly was maintained throughout evolution.
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PMID:The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. 1294 57

Normal metabolic balance is maintained by a complex homeostatic system involving multiple tissues and organs. Acquired or inherited defects associated to environmental factors in any part of this system can lead to metabolic disorders such as the syndrome X which is presently a frequent syndrome in industrialized countries. It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. Therapeutic intervention favours at present diet and exercise prescriptions. In addition, if necessary, specific treatment of the metabolic disorders is required. In the treatment of insulin resistance, new promising drugs are likely to be used in the next future. In this regard, adipose tissue, once thought to function primarily as a passive depot for the storage of excess lipid, is now understood to play a much more active role in metabolic regulation, secreting a variety of metabolic hormones and actively functioning to prevent deleterious lipid accumulation in other tissues and to modulate the insulin resistance. Here, we review new advances in our understanding of mechanisms leading to insulin resistance and type 2 diabetes from the perspective of the role and interactions of recently identified adipocyte-specific chemical messengers, the adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6, and resistin.
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PMID:[Adipocytokins, obesity and development of type 2 diabetes]. 1459 11

Circulating levels of the cytokine interleukin 6 (IL-6) are elevated in obesity, correlate with body mass index (BMI), and predict the development of type 2 diabetes mellitus (T2DM). A promoter polymorphism in the IL6 gene is associated with obesity, altered levels of insulin sensitivity, and T2DM. IL-6 exerts its effects by binding to the IL-6 receptor (IL-6R) and levels of IL-6R have been correlated with BMI. It is possible that IL6R variants may also be related to obesity, but to our knowledge, no study has yet examined this relationship. The objective of this study was to examine the relationship between genetic variants in the IL6R gene and obesity in Pima Indians, a population prone to excess adiposity. We sequenced 6kb of the IL6R gene, corresponding to all exons, exon-intron boundaries, and 2kb of promoter in 30 Pima Indians. We identified six single nucleotide polymorphisms (SNPs) in the IL6R gene: a predicted Asp --> Ala substitution at position 358, a variant in the 3'-untranslated region, and 4 intronic SNPs. All SNPs were in strong linkage disequilibrium (D' >/= 0.90) and varied in minor allele frequency from 0.33 to 0.48. Association between IL6R genotype and BMI (kg/m(2)) was assessed in approximately 700 nondiabetic, full-heritage Pima Indians. For each SNP, individuals carrying the variant allele had a higher mean BMI compared to those with the wild-type allele (range: [37.3+/-7.2-38.2+/-7.0] vs. [35.5+/-7.3-36.0+/-7.5]; P=0.02-0.004). Our findings suggest that genetic variants in the IL6R gene may play a role in susceptibility to obesity. Assessment of these SNPs in other populations will be useful to determine the magnitude of obesity risk.
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PMID:Variants in the interleukin 6 receptor gene are associated with obesity in Pima Indians. 1468 Sep 81


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