Correlation of high-sensitivity C-reactive protein and plasma fibrinogen with individual complications in patients with type 2 diabetes.

OBJECTIVE: We investigated the correlation between acute-phase reactants, ie, high-sensitivity C-reactive protein (hsCRP) or fibrinogen and diabetic complications. METHODS: In 73 patients with type 2 diabetes, we investigated associations between both markers and carotid artery intimal medial complex thickness (IMT), heart rate variability, or urinary albumin excretion (UAE). RESULTS: Log hsCRP and fibrinogen correlated significantly with each other (r = 0.3701, P = 0.0013). Fibrinogen correlated negatively with the coefficient of variation of RR intervals (CV(RR)) and positively with log UAE (r = -0.2433, P = 0.0381; r = 0.4815, P < 0.0001), while log hsCRP did not. Furthermore both log hsCRP and fibrinogen did not correlate with IMT. CONCLUSION: We concluded that despite their close correlation, fibrinogen compared with hsCRP might be closely associated with diabetic microangiopathy and that both markers might not correlate with IMT as a marker of macroangiopathy.

Relationships between heart rate variability and urinary albumin excretion in patients with type 2 diabetes.

BACKGROUND: Although in type 1 diabetes the close association between heart rate variability and urinary albumin excretion (UAE) is recognized even in patients with normoalbuminuria, this association has not yet been fully established in patients with type 2 diabetes. Therefore, we investigated the association in patients with type 2 diabetes. PATIENTS AND METHODS: All the hospital's 185 inpatients with type 2 diabetes were prospectively enrolled. Heart rate variability was evaluated by coefficients of variance of RR intervals (CVRR). RESULTS: The mean age, duration of diabetes, and hemoglobin A1C of the patients were 59.7+/-9.9 years, 10.4+/-7.8 years, and 9.7+/-2.3%, respectively. An analysis of the patients showed a significant negative correlation between CVRR and log10-transformed (log) UAE (R=-0.3340, P <0.0001). CVRR showed a significant negative correlation with age, duration of diabetes, hemoglobin AIC, systolic blood pressure, diastolic blood pressure, and triglyceride level. Log UAE showed a significant positive correlation with body mass index, hemoglobin A1C, systolic blood pressure, diastolic blood pressure, total cholesterol, and triglyceride level. In the macroalbuminuric group (UAE above 300 mg/g creatinine; n=57), although CVRR showed a significant negative correlation with log UAE (R=-0.3571, P= 0.0064), but in normoalbuminuric (UAE below 30 mg/g Cr; n=79) and in microalbuminuric groups (30 to 300 mg/g Cr; n = 49), CVRR and log UAE showed no correlation. CONCLUSIONS: Our data suggest that in type 2 diabetes, the association between CVRR and UAE is significant only in patients with macroalbuminuria.

Metabolic syndrome accompanied by hypercholesterolemia is strongly associated with proinflammatory state and impairment of fibrinolysis in patients with type 2 diabetes: synergistic effects of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor.

OBJECTIVE: To determine whether plasma concentrations of thrombin-activatable fibrinolysis inhibitor (TAFI) in patients with type 2 diabetes were associated with components of metabolic syndrome (MS), including high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI)-1, and LDL cholesterol. RESEARCH DESIGN AND METHODS: We studied 136 consecutive patients with type 2 diabetes. Diagnosis of MS was diagnosed by current criteria. Hypercholesterolemia (HC) was defined as serum LDL cholesterol >140 mg/dl (3.6 mmol/l) or treatment with a statin. For comparisons, diabetic patients were divided into four groups: those with no MS and no HC (n = 38), with MS but not HC (n = 39), with no MS but with HC (n = 26), and with both MS and HC (n = 33). RESULTS: Considering all patients with type 2 diabetes, plasma PAI-1 was strongly associated with MS components such as BMI, triglyceride, alanine aminotransferase, a homeostasis model assessment of insulin resistance, and hs-CRP. Plasma TAFI only correlated positively and independently with LDL cholesterol. Plasma concentrations of plasmin-alpha2-antiplasmin complex (PAP), a measure of fibrinolytic activity in blood, showed a significant negative correlation with plasma PAI-1 but not TAFI. Diabetic patients with both MS and HC had the highest serum hs-CRP concentrations and the lowest plasma PAP concentrations. CONCLUSIONS: LDL cholesterol is a main determinant of plasma TAFI in patients with type 2 diabetes. Coexistence of MS and HC synergistically accelerates inflammation and impairment of fibrinolysis via elevated concentrations of both TAFI and PAI-1, which inhibit fibrinolysis.

The effect of low-dose atorvastatin on circulating monocyte chemoattractant protein-1 in patients with type 2 diabetes complicated by hyperlipidemia.

The effect of low-dose atorvastatin on various biomarkers was investigated in patients with type 2 diabetes complicated by hyperlipidemia. At 0 and 12 weeks in both the atorvastatin group (10 mg/d; n=17) and the no-drug group (n=10), high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein (MCP)-1, plasminogen activator inhibitor (PAI)-1, and fibrinogen were measured. At baseline, the entire group of diabetic patients (n=27) had significantly higher values of hsCRP and fibrinogen compared with those in age-matched healthy subjects (n=29): 0.801 (0.306, 1.760) vs 0.282 (0.143, 0.6505) mg/L, P=.0042; 329.1+/-55.0 vs 212.4+/-35.9 mg/dL, P<.0001, respectively. High-sensitivity C-reactive protein decreased significantly with atorvastatin treatment, from 0.801 (0.243, 1.865) to 0.308 (0.200, 0.804) mg/L (P=.0191). Although MCP-1, PAI-1, and fibrinogen did not decrease in the atorvastatin patients overall, the decrease of MCP-1 was significant in women (n=10; from 241.9+/-45.8 to 215.4+/-49.5 pg/mL, P=.0332). No correlation was found between changes in the serum lipid concentrations and changes in hsCRP, MCP-1, PAI-1, or fibrinogen in either the atorvastatin or the no-drug group. In conclusion, low-dose atorvastatin (10 mg/d) significantly decreased hsCRP in patients overall, and MCP-1 was also decreased in women. These findings suggest the possibility that atorvastatin provides an anti-inflammatory effect even at a low dose.

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers effectively and directly potentiate superoxide scavenging by polymorphonuclear leukocytes from patients with type 2 diabetes mellitus.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) have potent antioxidant effects in addition to antihypertensive effects. METHODS: We investigated the ability of ACEIs and ARBs to enhance the superoxide scavenging ability of polymorphonuclear leukocytes (PMNLs) from type 2 diabetic patients (n = 32) and healthy subjects (n = 32). The scavenging ability (U/10(3) cells) of superoxide was measured by electron spin resonance. We used ascorbic acid as a positive control antioxidant and tested captopril, temocapril (an inactive form of ACEI), and temocaprilate (an active form of ACEI) as ACEIs, as well as RNH-6270 as an ARB. RESULTS: Captopril, temocaprilate, and RNH-6270 showed dose-dependent enhancement in scavenging ability. The scavenging ability with captopril and temocaprilate was greater than with RNH-6270. The changes in scavenging ability induced by all of the drugs in diabetic patients were similar to the changes in healthy subjects. A high-glucose medium (400-800 mg/dL) greatly attenuated the drug-induced enhancement of scavenging ability. CONCLUSIONS: We demonstrated that both ACEIs and ARBs enhance superoxide scavenging by PMNLs from type 2 diabetic patients and that a high-glucose environment markedly attenuates the ability of these drugs to augment superoxide scavenging.

Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia.

BACKGROUND: Diabetic nephropathy, especially when advanced, is associated with high prevalence of atherosclerotic cardiovascular disease in which inflammation and coagulation may play pathogenic roles. We investigated the relationships between diabetic nephropathy and coagulation, fibrinolysis, or inflammation in patients with Type 2 diabetes. METHODS: We evaluated markers of inflammation and coagulation in 105 Type 2 diabetic patients with various grades of nephropathy and 49 healthy control subjects, in association with plasma total homocysteine (tHcy) measurements. RESULTS: Plasma tHcy concentrations were significantly higher in diabetic patients than in controls (8.96 +/- 3.04 vs. 6.92 +/- 1.36 micromol/l, P < 0.0001). Plasma concentrations of interleukin (IL)-6 were significantly higher in diabetic patients than in control subjects (P < 0.0001). In diabetic patients, plasma tHcy correlated positively with urinary albumin, fibrinogen, IL-6 and plasmin-alpha2-antiplasmin complex (PAP), while plasma tHcy correlated negatively with creatinine clearance (Ccr) and protein C activity. After adjustment for Ccr, IL-6 and protein C activity were significantly associated with plasma tHcy. Plasma tHcy concentrations were significantly higher in patients with overt albuminuria than in those with normoalbuminuria or microalbuminuria, as were plasma concentrations of fibrinogen, prothrombin F1+2, and interleukin-6. CONCLUSIONS: Diabetic nephropathy is associated with elevated markers for both coagulation and inflammation. High plasma homocysteine may be a link between diabetic nephropathy and both chronic inflammation and hypercoagulability, increasing cardiovascular risk.

Association between the corrected QT intervals and combined intimal-medial thickness of the carotid artery in patients with type 2 diabetes.

The main purpose of this study was to determine whether cardiac autonomic neuropathy or coronary atherosclerosis is the more important factor affecting prolongation of the corrected QT interval (QTc) in patients with type 2 diabetes. We studied the association between QTc and the coefficient of variance of the heart rate variation (CV(RR)), which reflects cardiac autonomic neuropathy, and the combined intimal-medial thickness (IMT) of the common carotid artery, which reflects coronary atherosclerosis. In addition, we also investigated the relationship between the QTc and blood pressure, serum lipid concentrations, hemoglobin A(1C) (HbA(1C)) concentration, and duration of diabetes. We studied 75 patients with type 2 diabetes and 30 age-matched healthy individuals. The QT interval was measured in lead II of the electrocardiogram (ECG) and was corrected using Bazett's formula. Cardiac neuropathy was assessed by measuring CV(RR). Atherosclerosis was evaluated by measuring the combined IMT of the common carotid artery using B-mode ultrasonography. The QTc in patients with type 2 diabetes was significantly longer than in healthy individuals (P <.0001). The QTc more closely correlated with the IMT of the carotid artery (r = 0.7206, P <.0001), compared with CV(RR) (r = -0.3188, P =.0053), although both were statistically significant. The QTc also correlated positively with the systolic (SBP) and diastolic blood pressure (DBP) (r = 0.4371, P <.0001, r = 0.3632, P =.0014, respectively). Based on stepwise regression analysis with the QTc interval as the dependent variable, the IMT of the carotid artery had the most significant association with the QTc (beta = 0.6882, P =.0004). In conclusion, QTc prolongation in the setting of diabetes might be caused primarily by coronary atherosclerosis rather than by cardiac autonomic neuropathy.

Measles encephalitis and acute pancreatitis in a young adult.

Although rare, encephalitis and hepatitis are major complications of measles that are more common in adults than in infants. On the other hand, although several other complications of measles, such as pneumonia and myocarditis, are found in all ages, acute pancreatitis in measles is very rare in both children and adults. We describe a 16-year-old female patient with measles encephalitis who developed acute pancreatitis. The response to steroid therapy was favorable.

Results of blood inflammatory markers are associated more strongly with toe-brachial index than with ankle-brachial index in patients with type 2 diabetes.

OBJECTIVE: Three blood markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin [IL]-6, and fibrinogen) were compared with markers of atherosclerotic cardiovascular disease (CVD) (history of stroke or cardiac ischemia and measured toe-brachial index [TBI]) to determine whether inflammatory markers are associated with atherosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Of 103 patients with type 2 diabetes, 26 had CVD. TBI was plethysmographically determined in both great toes. Serum hsCRP was immunonephelometrically determined. Plasma IL-6 was measured by an enzyme immunoassay. RESULTS: Both ABI and TBI were lower in diabetic patients with CVD than in those without CVD (1.05 +/- 0.19 vs. 1.14 +/- 0.09, P < 0.05, and 0.75 +/- 0.20 vs. 0.95 +/- 0.21, P < 0.001, respectively). By linear regression, right TBI but not right ABI showed a significant negative correlation with serum hsCRP (r = -0.372, P < 0.01) and plasma fibrinogen (r = -0.224, P < 0.05). Serum hsCRP was also negatively correlated with lower TBI, but not lower ABI. We found no significant correlation between plasma IL-6 and ABI or TBI. CONCLUSIONS: TBI was strongly associated with CVD, serum hsCRP, and plasma fibrinogen. Of these inflammatory markers, serum hsCRP may be the most promising marker for vascular inflammation.