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)

Microalbuminuria is a novel atherosclerotic risk factor in patients with type 2 diabetes mellitus (DM) and predicts future cardiovascular events. Endothelial dysfunction and systemic inflammation have been proposed as common links between microalbuminuria and cardiovascular disease. However, no study has assessed the relation between microalbuminuria and vascular dysfunction as measured by brachial artery reactivity (BAR) in DM. We evaluated 143 patients (85 men; mean age 60.0 +/- 6.7 years) with DM (mean duration 8.2 +/- 7.4 years) enrolled in the Detection of Ischemia in Asymptomatic Diabetics study. Subjects were categorized as those with microalbuminuria (ratio of urinary albumin to creatinine 30 to 299 microg/mg creatinine, n = 28) and those with normoalbuminuria (ratio of urinary albumin to creatinine 0 to 29.9 microg/mg creatinine, n = 115). High-resolution ultrasound BAR testing was used to measure endothelium-dependent and endothelium-independent vasodilations. C-reactive protein was measured as a marker of systemic inflammation. Patients with microalbuminuria and normoalbuminuria had similar baseline characteristics, with the exception that those with microalbuminuria had a longer duration of DM (p = 0.03). Endothelium-dependent vasodilation at 1 minute (p = 0.01) and endothelium-independent vasodilation at 3 minutes (p = 0.007) were significantly less in patients with microalbuminuria. In addition, 96% of patients with microalbuminuria and 76% of those with normoalbuminuria had impaired endothelium-dependent vasodilation (<8%, p = 0.01). Microalbuminuria was an independent predictor of endothelium-dependent vasodilation in the entire cohort (p = 0.045) and after excluding patients on hormone replacement therapy (p = 0.01). Levels of C-reactive protein were significantly higher in patients with microalbuminuria than in those with normoalbuminuria (p = 0.02). We conclude that in DM the presence of microalbuminuria is associated with impaired endothelium-dependent and endothelium-independent vasodilations of the brachial artery and a higher degree of systemic inflammation. In addition, microalbuminuria is an independent predictor of endothelial dysfunction in asymptomatic patients with DM, especially in the absence of hormone replacement therapy.
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PMID:Brachial artery reactivity in asymptomatic patients with type 2 diabetes mellitus and microalbuminuria (from the Detection of Ischemia in Asymptomatic Diabetics-brachial artery reactivity study). 1527 91

Patients with end-stage renal disease (ESRD) are at high risk from potentially devastating cardiovascular sequelae due to the unique clustering of risk factors in these patients. Inflammation is believed to play a key role in the pathogenesis of these cardiovascular lesions. Both pro- and anti-inflammatory cytokines produced from monocytes, and also from adipocytes, have been studied in this regard. Pro-inflammatory cytokines, although cytoprotective acutely, correlate with increased risk of cardiovascular disease (CVD) in chronic situations. Conversely, elevated levels of anti-inflammatory mediators are associated with increased patient survival times. Statistical modelling, calculation of relative risk and cost considerations indicate that determination of serum C-reactive protein levels may be a useful predictor of CVD in ESRD patients. Adipocytes are a rich source of many of the same cytokines produced by monocytes, including interleukin-6, tumour necrosis factor-alpha, as well as adipocyte-specific proteins, leptin and adiponectin (ADPN). ADPN, which is produced in much greater quantities than leptin, is inversely related to body mass index and to insulin resistance, suggesting a possible role in type 2 diabetes. Additionally, ADPN has been shown to modulate the endothelial inflammatory response in vitro. Plasma ADPN levels are an inverse predictor of cardiovascular outcomes among patients with ESRD. Furthermore, ADPN is related to several metabolic risk factors in a manner consistent with the hypothesis that this protein acts as a protective factor for the cardiovascular system.
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PMID:Inflammatory proteins as predictors of cardiovascular disease in patients with end-stage renal disease. 1528 63

Leptin signaling may promote atherothrombosis and lead to cardiovascular disease. However, whether leptin is associated with human atherosclerosis, distinct from thrombosis, is unknown. We determined the association of plasma leptin levels with coronary artery calcification (CAC), a measure of coronary atherosclerosis, in a cross-sectional study of type 2 diabetes. Leptin levels were associated with CAC after adjusting for established risk factors [odds ratio (95% confidence interval) for 5 ng/ml leptin increase: 1.31 (1.10-1.55); P = 0.002]. Leptin remained associated with CAC after further controlling for body mass index (BMI) [1.29 (1.07-1.55); P = 0.008], waist circumference [1.30 (1.09-1.57); P = 0.003], C-reactive protein (CRP) levels [1.28 (1.07-1.55); P = 0.008], and subclinical vascular disease [1.30 (1.08-1.57); P = 0.006]. Addition of BMI (P = 0.97), waist (P = 0.55), or CRP (P = 0.39) to a model with leptin failed to improve the model's explanatory power, whereas addition of leptin to a model with BMI (P = 0.029), waist (P = 0.006), or CRP (P = 0.005) improved the model significantly. Plasma leptin levels were associated with CAC in type 2 diabetes after controlling adiposity and CRP. Whether leptin signaling promotes atherosclerosis directly or represents a therapeutic target for the prevention of atherosclerotic cardiovascular disease remains to be explored.
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PMID:Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes. 1529 20

Impairment of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear receptor that regulates genes involved in lipid and glucose metabolism, may contribute to the onset of metabolic disorders such as diabetes and the accompanying dyslipidemia. Fat-derived tumor necrosis factor alpha (TNF-alpha) and the acute-phase response protein, C-reactive protein (CRP), may also have a role in the development of obesity-related insulin resistance and type 2 diabetes mellitus. In this study, a group of 14 naturally occurring, insulin-requiring, type 2 diabetic cynomolgus monkeys were used to evaluate the effects of the PPAR-gamma agonist, rosiglitazone, on glycemic and lipid parameters and serum levels of TNF-alpha and CRP. The animals were randomized into 2 groups of 7. One group was treated with 0.5 mg/kg rosiglitazone orally once a day for 7 weeks. Blood was collected for evaluation at baseline, at 2 and 7 weeks during the treatment period, and at 7 and 13 weeks after treatment. Daily insulin requirements were recorded during the entire study. Results showed daily exogenous insulin requirements were significantly reduced (P <.01) in those treated with rosiglitazone, while glycemic control was maintained. Plasma triglyceride concentrations were significantly lower (P <.01) whereas plasma cholesterol levels tended to be lower and high-density lipoprotein (HDL) concentrations tended to be higher after treatment. No significant differences were noted in TNF-alpha and CRP serum levels during the treatment period. Body weights remained steady in both groups during the study. These results suggest overall improvement in insulin regulation and lipid profiles during treatment with rosiglitazone.
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PMID:Rosiglitazone treatment improves insulin regulation and dyslipidemia in type 2 diabetic cynomolgus monkeys. 1533 71

Low-grade systemic inflammation is associated with an increased risk of type 2 diabetes mellitus. Limited available data suggest inflammatory factors are predictive of gestational diabetes (GDM), a condition that is biochemically similar to type 2 diabetes. We examined the association between C-reactive protein (CRP) and GDM risk. Women were recruited before 16 weeks gestation and were followed until delivery. Maternal serum CRP (collected at 13 weeks' gestation, on average) was measured by a competitive immunoassay. We used generalised linear models to derive estimates of relative risks and 95% confidence intervals [CI]. Approximately 4.5% of the cohort (38 of 851) developed GDM. Elevated CRP was positively associated with GDM risk (P for trend = 0.007). After adjusting for maternal prepregnancy body mass index (BMI), family history of type 2 diabetes and nulliparity, women with CRP in the highest tertile experienced a 3.5-fold increased risk of GDM [95% CI 1.2, 9.8] as compared with those in the lowest tertile. The association between CRP and GDM was evident when analyses were restricted to lean women (BMI < 25 kg/m(2)). Lean women with CRP > or = 5.3 mg/L experienced a 3.7-fold increased risk of GDM [95% CI 1.6, 8.7] as compared with women with CRP < 5.3 mg/L. Systemic inflammation is associated with an increased risk of GDM, and the association is independent of maternal prepregnancy adiposity.
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PMID:A prospective study of maternal serum C-reactive protein (CRP) concentrations and risk of gestational diabetes mellitus. 1536 25

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

Elevated C-reactive protein (CRP) levels have previously been described before the onset of type 2 diabetes and gestational diabetes. We hypothesized that inflammation, as reflected by elevated CRP levels, can help predict development of islet autoimmunity or type 1 diabetes. Children at risk for type 1 diabetes and followed in the Diabetes Autoimmunity Study of the Young (DAISY) had blood samples drawn and frozen serum saved at various intervals after birth. CRP was measured using a high-sensitivity sandwich enzyme immunoassay. Islet autoantibodies (IAs) were measured using biochemical immunoassays. Elevations in CRP concentrations were significantly more frequent (P < 0.01) in children who later developed type 1 diabetes (8 of 16 children) than in children negative for IAs at their last testing (3 of 26). Children with one or more positive IA were more likely to have elevated CRP concentrations (15 of 36) than IA-negative children (3 of 26; P < 0.01). The finding of elevated CRP levels in infants and young children before the onset of type 1 diabetes adds to the evidence that the disease is an immunoinflammatory disorder. The elevated CRP levels may provide an additional marker for risk of progression to type 1 diabetes.
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PMID:Elevated C-reactive protein levels in the development of type 1 diabetes. 1544 85

A limited number of studies have reported associations of markers of liver injury, including elevated concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with prospective risk of type 2 diabetes. However, only one study has adjusted for a detailed measure of insulin sensitivity (insulin sensitivity index [S(i)]), which is important given associations of obesity and S(i) with nonalcoholic fatty liver disease (NAFLD). Our objective was to investigate the associations of elevated AST and ALT with incident type 2 diabetes among 906 participants in the Insulin Resistance Atherosclerosis Study who were nondiabetic at baseline. S(i) and acute insulin response (AIR) were measured directly from the frequently sampled intravenous glucose tolerance test among black, Hispanic, and non-Hispanic white participants aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes. Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22 and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and fasting glucose (r = 0.13 and r = 0.29) and inversely with S(i) (r = -0.18 and r = -0.30; all P < 0.0001). In separate logistic regression models adjusting for age, sex, ethnicity, clinical center, and alcohol consumption, participants in the highest quartiles (Q4) of AST and ALT were at significantly increased risk of incident type 2 diabetes compared with those in the lowest three quartiles (Q1-Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75). After further adjustment for smoking, waist circumference, triglyceride, HDL, impaired glucose tolerance, S(i), and AIR, both AST and ALT remained significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR 1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no interactions of sex, ethnicity, obesity, impaired glucose tolerance, or S(i) with AST or ALT in the prediction of type 2 diabetes. When entered into the same model with adjustment for demographic variables, both C-reactive protein and ALT independently predicted type 2 diabetes. In addition, AST and ALT were positively associated with incident type 2 diabetes after excluding former and moderate to heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes. Baseline elevations of these markers may reflect NAFLD or related pathologies.
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PMID:Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study. 1544 93

The objective of the study was to determine whether plasma migration inhibitor factor (MIF) concentration and mononuclear cell (MNC) mRNA are elevated in obesity and whether treatment with metformin reduces plasma MIF concentration. Forty obese subjects [body mass index (BMI), 37.5 +/- 4.9 kg/m(2)] and 40 nonobese healthy subjects (BMI, 22.6 +/- 3.4 kg/m(2)) had their plasma MIF, glucose, insulin, free fatty acids (FFAs) and C-reactive protein (CRP) concentrations measured. Sixteen obese patients and 16 nonobese healthy subjects had RNA prepared from MNCs. Eight obese subjects with normal glucose concentration were treated with metformin 1 g (Glucophage XR; 1000 mg twice daily) twice daily for 6 wk. Eight obese subjects were used as controls. Plasma concentration of glucose, insulin, FFAs, and MIF was measured by appropriate assays. mRNA for MIF was measured by real-time PCR. Forty obese subjects had a fasting concentration of MIF of 2.8 +/- 2.0 ng/ml, whereas 40 nonobese subjects had a fasting MIF concentration of 1.2 +/- 0.6 ng/ml (P < 0.001). Plasma MIF concentrations were significantly related to BMI (r = 0.52; P < 0.001). mRNA for MIF was correlated to plasma FFAs (r = 0.40; P < 0.05) and plasma CRP (r = 0.42; P < 0.05) concentrations. Eight obese subjects had their fasting blood samples taken before and after taking a slow-release preparation of metformin at 1, 2, 4, and 6 wk. The mean plasma concentration fell from 2.3 +/- 1.4 to 1.6 +/- 1.2 ng/ml at 6 wk (P < 0.05). Obese subjects not on treatment with metformin showed no change. During the period of treatment with metformin, the body weight did not change and the plasma concentration of glucose, insulin, and FFAs did not alter. We conclude that: 1) plasma MIF concentrations and MIF mRNA expression in the MNCs are elevated in the obese, consistent with a proinflammatory state in obesity; 2) these increases in MIF are related to BMI, FFA concentrations, and CRP; 3) metformin suppresses plasma MIF concentrations in the obese, suggestive of an antiinflammatory effect of this drug; and 4) this action of metformin may contribute to a potential antiatherogenic effect, which may have implications for the reduced cardiovascular mortality observed with metformin therapy in type 2 diabetes mellitus.
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PMID:Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. 1547 3

Most studies describe the association between one particular inflammatory marker and insulin resistance (IR), features of the metabolic syndrome, or progression to type 2 diabetes. We aimed to build an Inflammation Score as a tool to measure IR-associated inflammatory activity and to evaluate the ability of different surrogate indexes of IR to reflect the inflammatory state. We studied 81 subjects, aged 47.7 +/- 12 yr with a body mass index of 28.3 +/- 4 kg/m(2). The Inflammation Score was composed of: white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and soluble fraction of TNF-alpha receptors 1 and 2. All the subjects underwent a frequently sampled iv glucose tolerance test, an oral glucose tolerance test, and surrogate indexes of IR were calculated. Each increase in the Inflammation Score was associated with a progressive increase in IR. We found significant differences across categories (0-1, 2, 3, and 4-5 points in the score) in age (P = 0.048), waist circumference (P = 0.015), body mass index (P = 0.013), blood pressure (P = 0.005), and uric acid (P = 0.031). The Inflammation Score was significantly associated with all but three of the surrogate IR indexes [2-h insulin glucose ratio, Gutt's insulin sensitivity (SI) index, and Avignon's 2-h SI index]. Surrogate indexes obtained from basal values showed a similar correlation with the Inflammation Score than the SI from frequently sampled iv glucose tolerance test. In summary, the Inflammation Score is a useful tool in the evaluation of IR-associated inflammatory activity. The surrogate indexes obtained using fasting glucose and insulin appear to better reflect this inflammatory state. Basal rather than stimulated indexes should be used in the evaluation of therapeutic measures aimed at modifying IR-associated inflammatory activity.
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PMID:An inflammation score is better associated with basal than stimulated surrogate indexes of insulin resistance. 1548 52


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