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)

Considerable evidence supports a major inherited component of type 2 diabetes. We initially conducted a genome-wide scan with 440 microsatellite markers at 10-cM intervals in 19 multigenerational families of Northern European ancestry with at least two diabetic siblings. Initial two-point analyses of these families directed marker typing of 23 additional families. Subsequently, all available marker data on the total of 42 families were analyzed using both parametric and nonparametric multipoint methods to test for linkage to type 2 diabetes. One locus on chromosome 1q21-1q23 met genome-wide criteria for significant linkage under a model of recessive inheritance with a common diabetes allele (logarithm of odds [LOD] = 4.295). Both pedigree-based nonparametric linkage (NPL) analysis and affected sib pair (MAPMAKER/SIBS) nonparametric methods also showed the highest genome-wide scores at this region, near markers CRP and APOA2, but failed to meet levels of genome-wide significance. The risk of type 2 diabetes to siblings of a diabetic person when compared with the population (lambdaS) was estimated from MAPMAKER/SIBS to be 2.8 in these 42 families. Simulation studies using study data confirmed a genome-wide significance level of P<0.05 (95% CI 0.005-0.0466). However, analysis of 20 similarly ascertained but smaller families failed to confirm this linkage. The LOD score with 50% heterogeneity for all 62 families considered together was only 2.25, with an estimated lambdaS of 1.87. Our data suggest a novel diabetes susceptibility locus near APOA2 on chromosome 1 in a region with many transcribed genes.
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PMID:A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians. 1033 26

The possible role of inflammation in coronary artery disease (CAD) is being recognised, while markers of inflammation (e.g., CRP) and infection with Chlamydia pneumoniae (C. pneumoniae), cytomegalovirus (CMV) and Helicobacter pylori (H. pylori) have been proposed as risk factors for CAD. However, these associations require further evaluation. It is a known fact that diabetic patients suffer from impaired immune response to some pathogens and a high incidence of atherosclerosis. In this case-control study we investigated serological markers of infection with C. pneumoniae, CMV, and H. pylori in a group of 140 patients with unstable angina pectoris (UA), 52 of them having type 2 diabetes mellitus, and in a matched control group. Anamnestic (IgG) and acute infection (IgA) antibodies against the above agents were tested using ELISA or indirect immunofluorescence tests. In patients with UA we found a significantly higher seroprevalence and titres of IgG antibodies against C. pneumoniae (p = 0.04) and increased titres of IgG antibodies against CMV (p = 0.007). No differences were found in IgA antibody response to these pathogens. Antibody response to H. pylori was similar in both groups tested. In diabetic patients with UA, the frequency of group-common IgG antibodies against C. pneumoniae was higher than in the non-diabetic UA patients. The other serological markers studied were comparable in the patients with or without diabetes mellitus. Our findings confirmed association of C. pneumoniae and CMV with cardiovascular heart disease. Moreover, diabetes mellitus may predispose the patients to C. pneumoniae infection. However, serological markers observed do not indicate that destabilisation of angina pectoris is associated with acute C. pneumoniae or CMV infection. No relationship was found between UA and H. pylori infection.
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PMID:Serological markers of Chlamydia pneumoniae, cytomegalovirus and Helicobacter pylori infection in diabetic and non-diabetic patients with unstable angina pectoris. 1288 57

Proinflammatory state may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease observed in populations originating from the Indian subcontinent (Asian Indians). This study was conducted to evaluate whether nondiabetic Asian Indian men living in the United States manifest a proinflammatory state when compared with Caucasians of similar age and body fat content. We also compared the relationships between plasma high-sensitivity C-reactive protein (hs-CRP), a marker of low-grade inflammation, and various parameters of body composition and fat distribution and insulin sensitivity in Asian Indians and Caucasians. For this purpose, plasma hs-CRP, oral glucose tolerance test, and anthropometric measurements were conducted in 82 Asian Indian men and 55 Caucasian men of similar age. The two groups had similar body fat content and truncal skinfolds thickness. Asian Indians had higher insulin areas under the curve during oral glucose tolerance tests, indicating a greater insulin resistance. Asian Indians also manifested a significant elevation of plasma hs-CRP. We conclude that young, overtly healthy Asian Indian men have both greater insulin resistance and higher hs-CRP levels than do Caucasians. This difference cannot be explained by greater adiposity in Asian Indians and suggests that many Asian Indians have an underlying proinflammatory state that may contribute to their increased risk for both type 2 diabetes and cardiovascular disease.
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PMID:Elevated plasma high-sensitivity C-reactive protein concentrations in Asian Indians living in the United States. 1291 68

Insulin resistance (IR)/hyperinsulinemia and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP]) can predict cardiovascular disease. However, because IR and inflammation (IF) have not been evaluated simultaneously, it is not known whether IR and IF are independently related to cardiovascular disease. Furthermore, the combined effect of IR and IF on the prediction of cardiovascular disease is presently unknown. Thus, we measured insulin sensitivity (K index of the insulin tolerance test; KITT) and hs-CRP in 350 Japanese patients with type 2 diabetes, and followed them for 1-7 years (mean, 4.5 years). During the follow-up, 33 patients died and 53 patients developed non-fatal coronary artery disease or stroke (endpoint). Age, systolic blood pressure, current smoking, past history of cardiovascular disease, KITT, and hs-CRP independently and significantly correlated with endpoint. One-S.D. difference was associated with a significant increase of relative risk in KITT (1.45; 95% CI 1.09-1.91) and hs-CRP (1.30; 1.04-1.67). When patients were subdivided to tertile, the relative risk in the highest tertile of KITT was 1.76 (95% CI 1.01-3.11) and hs-CRP was 2.00 (1.03-3.85) compared with the patients with lowest tertile. The relative risk in the highest tertile of both KITT and hs-CRP was 5.32 (1.18-24.0) compared with the lowest tertile of both values. In conclusion, low-grade IF and IR are independently related to all-cause of death and cardiovascular disease in Japanese patients with type 2 diabetes. Coexistence of low-grade IF and IR amplify this effect.
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PMID:Inflammation and insulin resistance are independently related to all-cause of death and cardiovascular events in Japanese patients with type 2 diabetes mellitus. 1292 84

The beta(2)-adrenergic receptor (B2AR) is expressed in pancreatic beta-cells and modulates insulin secretion. The purpose of the present study was to evaluate the influence of the Arg16Gly variant allele of B2AR on insulin secretion in patients with type 2 diabetes. We used minimal model analysis of the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) and polymerase chain reaction (PCR)-restriction fragment length polymorphism to examine differences of insulin secretion and insulin resistance among three genotypes. There were no significant differences in baseline clinical characteristics, HbA1c, uric acid, CRP or lipid profiles among the three groups. The Gly/Gly group had significantly higher levels of fasting insulin (38.2+/-4.7 pmol/l versus 23.6+/-3.5 pmol/l) and homeostasis model assessment of insulin resistance (HOMA-R) (1.90+/-0.19 versus 1.32+/-0.24), compared with the Arg/Arg group, but there were no significant differences in acute insulin response to glucose (AIRg) bolus, insulin sensitivity (Si), or glucose effectiveness (Sg) among the three genotypes. Several reports have speculated that the Gly16 allele of B2AR exhibits agonist-promoted downregulation, but our findings, elevated fasting insulin concentrations, and previous clinical studies of blood pressure and lypolysis are controversial. The direct mechanism by which the Gly16 allele of B2AR may influence insulin secretion of pancreatic beta-cells is unknown. Further studies of the expression of the allelic receptor in islet cells may help to resolve the role of B2AR in insulin secretion. However, increased sensitivity to catecholamine-induced lipolysis of the Gly allele promotes higher free fatty acids concentrations in the portal system, which could enhance the higher levels of fasting insulin.
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PMID:Genotype Gly/Gly of the Arg16Gly polymorphism of the beta2-adrenergic receptor is associated with elevated fasting serum insulin concentrations, but not with acute insulin response to glucose, in type 2 diabetic patients. 1469 8

Obesity is a risk factor for type 2 diabetes and cardiovascular diseases. The hypothesis that cytokines could play a role in the pathophysiology of obesity and insulin resistance is suggested in the last few years. We showed a positive correlation between circulating interleukin (IL-6) levels and obesity and insulin resistance suggesting that IL-6 could be involved in insulin resistance in humans. We showed a decrease of both circulating and adipose tissue IL-6 levels in non-diabetic obese subjects after a very low calorie diet program inducing weight loss. This suggests that adipose tissue could be involved in the regulation of circulating IL-6 levels in these subjects. Adipose tissue is also involved in lipodystrophies particularly in HIV patients on antiviral therapy. We showed an alteration of the SREBP-1 transcription step in subcutaneous abdominal adipose tissue from HIV patients. We found an inverse correlation between circulating adiponectin levels and both insulin resistance and cardiovascular risk factors such as CRP levels and apolipoprotein B/A1 ratio. These findings suggest that adipose tissue is involved in insulin resistance in humans particularly via adipocytokine secretion.
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PMID:[Insulin resistance and adipose tissue gene expression in humans]. 1504 87

Adiponectin has been identified as one of the "adipocytokines" that are derived only from adipose tissue, and are abundantly present in circulating blood. Adiponectin has protective actions in the initiation and progression of atherosclerosis through anti-inflammatory and anti-atherogenic effects. Adiponectin levels are decreased in obesity, type 2 diabetes, and patients with coronary artery disease (CAD). Adiponectin levels were negatively correlated with the CRP levels in patients with CAD. Adiponectin plays a crucial role in the association between obesity, type 2 diabetes, and insulin resistance. Mechanisms explaining the relationship between adiponectin and insulin resistance suggest that adiponectin and tumor necrosis factor (TNF)-alpha inhibited each other's expression and production in adipocytes. Thiazolidinediones, which are insulin-sensitizing agents, increased the production of adiponectin through directly enhancing its gene expression. The C-terminal globular domain of adiponectin may play a central role in the protective effects against atherosclerosis. Adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) are expressed ubiquitously in most organs, especially in skeletal muscle in AdipoR1, and liver in AdipoR2. With the prospect of future basic and clinical research on the molecular structure-receptor relationship, adiponectin could become a promising target for future investigations in reducing the morbidity and mortality of atherosclerotic disease.
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PMID:Adiponectin and atherosclerotic disease. 1514 66

High-sensitivity C-reactive protein (hs-CRP) levels are closely associated with adiposity and predict coronary heart disease and type 2 diabetes mellitus. However, relationships of CRP to adiponectin and other markers of insulin resistance have been inadequately researched in children. We measured fasting serum levels of adiponectin, insulin, hs-CRP, and lipoproteins, and recorded the anthropometric profile and percentage of body fat (%BF; bioimpedance method) in 62 (36 normal weight, 26 overweight) healthy, urban, postpubertal Asian Indian males (aged 14 to 18 years). Serum levels of adiponectin were lower (P = not significant [NS]), whereas those of fasting insulin (P = .01) and hs-CRP (P = .02) were higher in overweight subjects. Adiponectin levels inversely correlated with body mass index (BMI; r = -0.26, P < .05), %BF (r = -0.24, P < .05), fasting insulin (r = -0.32, P < .05) and insulin resistance measured by the homeostasis model of assessment (HOMA-IR; r = -0.31, P < .05), but not with hs-CRP levels. Fasting insulin and hs-CRP levels correlated significantly with BMI, %BF, waist circumference (WC), waist-to-hip circumference ratio (W-HR), and triceps and subscapular skinfold thickness. The correlation of adiponectin with insulin sensitivity was independent of abdominal obesity, but became nonsignificant after controlling for BMI and %BF. Further, BMI was an independent predictor of adiponectin levels and the ratio of adiponectin and %BF was an independent predictor of fasting insulin levels. Although adiponectin levels did not correlate with hs-CRP levels, we observed dichotomous relationships of adiponectin and hs-CRP levels with generalized and abdominal obesity, respectively. We conclude that generalized obesity affects the adiponectin-insulin relationship in postpubertal Asian Indian males; however, the relationship of adiponectin with hs-CRP needs further evaluation.
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PMID:Adiponectin, insulin resistance, and C-reactive protein in postpubertal Asian Indian adolescents. 1537 91

Central obesity, insulin resistance, inflammation, as well as vascular changes are common in patients with type 2 diabetes. In this study we assessed the relationship among stiffness of the carotid artery, visceral fat, and circulating inflammatory markers in type 2 diabetic subjects. Carotid stiffness, quantified as the distensibility coefficient (DC), was measured by ultrasound in asymptomatic, normotensive patients with uncomplicated, well-controlled type 2 diabetes and in controls. Body fat distribution was quantified by magnetic resonance imaging. In patients, the carotid DC was inversely associated with visceral fat area (r = -0.660; P = 0.005) and plasma levels of C-reactive protein (CRP; r = -0.687; P = 0.002), but most strongly with plasma IL-6 (r = -0.766; P < 0.001). In multivariate analysis, the association between DC and visceral fat disappeared after adjustment for CRP and IL-6. Correction for age, body mass index, blood pressure, glycosylated hemoglobin, or fasting plasma glucose did not affect the association between carotid DC and inflammatory markers. Thus, carotid stiffness is associated with visceral obesity in patients with uncomplicated type 2 diabetes, but this association seems to be mediated by circulating IL-6 and CRP, of which IL-6, at least in part, originates from adipose tissue and stimulates hepatic CRP production.
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PMID:The association between abdominal visceral fat and carotid stiffness is mediated by circulating inflammatory markers in uncomplicated type 2 diabetes. 1561 16

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


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