C-reactive protein, its role in inflammation, Type 2 diabetes and cardiovascular disease, and the effects of insulin-sensitizing treatment with thiazolidinediones.

Increased concentrations of the marker of inflammation, C-reactive protein (CRP), are associated with insulin resistance, Type 2 diabetes and the development of cardiovascular disease. In particular, inflammation is closely associated with endothelial dysfunction and is recognized as one of the cardiovascular risk factors clustering in the Insulin Resistance Syndrome or Metabolic Syndrome. The exact mechanisms linking insulin resistance and inflammation remain unclear. However, the close association between insulin resistance and inflammation in atherogenesis suggests that therapies that address both parameters may have benefits in reducing diabetes-related macrovascular complications. The thiazolidinedione class of oral anti-diabetic agents are powerful insulin sensitizers that also have anti-inflammatory properties. Treatment with these agents has a range of anti-atherogenic effects, including reduced levels of CRP, plasminogen activator inhibitor-1 (PAI-1), TNF-alpha and reactive oxygen species. Additionally, the insulin-sensitizing effect of thiazolidinediones improves other factors of the Insulin Resistance Syndrome, including dyslipidaemia and hypertension. Outcome studies are underway to determine if the effects of improving insulin sensitivity and reducing inflammation will translate into clinical benefits and reduce the cardiovascular morbidity and mortality associated with insulin resistance and Type 2 diabetes.     

Prevalence and management of hypertension among Turkish, Moroccan and native Dutch ethnic groups in Amsterdam, the Netherlands: The Amsterdam Health Monitor Survey

OBJECTIVE: To assess ethnic differences in the prevalence and management of hypertension among Turkish, Moroccan and native Dutch ethnic groups in Amsterdam, the Netherlands. DESIGN: A cross-sectional survey. PARTICIPANTS: A random sample of 1304 adults aged 18 years and over. Of these, 39.2% were Dutch, 33.2% were Turkish and 27.6% were Moroccan. RESULTS: The prevalence of hypertension was lower in Turkish (men 25.8% and women 22.2%) and Moroccan (men 26.1% and women 19.6%) than in Dutch individuals (men 48.8% and women 35.0%). Except for Turkish women, these differences persisted after adjustment for age and body mass index: the odds ratios (95% confidence interval) for being hypertensive were 0.47 (0.30-0.74; P < 0.001) for Turkish men, 0.48 (0.30-0.76; P < 0.001) for Moroccan men and 0.51 (0.28-0.94; P = 0.03) for Moroccan women. Only Moroccan hypertensive women were less likely than Dutch women to be aware of their condition 0.31 (0.11-0.81; P < 0.01) and to be treated 0.32 (0.12-0.88; P < 0.01) for hypertension. There were no differences in hypertension control between the ethnic groups in both men and women. CONCLUSION: The lower prevalence of hypertension among Moroccan men may contribute to the low cardiovascular disease (CVD) mortality reported among this group in the Netherlands. The differential risks in CVD mortality between Moroccan men and women may partly result from the lower hypertension awareness and treatment rates in Moroccan women. Strategies aimed at improving the detection and treatment of hypertension among Moroccan women may improve the sex disparity in cardiovascular mortality between Moroccan men and women in the Netherlands.     

Increased activation of protein C, but lower plasma levels of free, activated protein C in uraemic patients: relationship with systemic inflammation and haemostatic activation

Chronic renal failure (CRF) courses with both systemic inflammatory reaction and haemostatic activation. We explored the relationship of these processes with plasma levels of free, activated protein C (APC) and complexes of APC with its inhibitors in patients with CRF under conservative treatment. Plasma concentrations of inflammatory cytokines [tumour necrosis factor alpha (TNFalpha) and interleukin 8], acute-phase proteins (C-reactive protein, fibrinogen, alpha1-anti-trypsin and von Willebrand factor), and markers of haemostatic activation (thrombin-anti-thrombin complexes, plasmin-anti-plasmin complexes, and fibrin and fibrinogen degradation products) were higher in patients than in controls. Inflammatory and haemostatic markers were significantly and positively correlated. Total plasma APC and APC:alpha1-anti-trypsin (alpha1AT) complexes were 44% and 75% higher in patients than in controls (P = 0.0001), whereas free APC was 20% lower (P < 0.015). No significant difference was observed in APC:protein C inhibitor (PCI) complexes between both groups. The free/total APC ratio was significantly lower in patients than in controls (P < 0.0001). Total plasma APC and APC:alpha1AT were positively correlated with activation markers of haemostasis and acute-phase proteins, whereas free APC was inversely correlated with plasma levels of creatinine, acute-phase proteins and fibrin degradation products (FnDP). Systemic inflammation and activation of haemostasis are interrelated processes in CRF. APC generation was increased in response to elevated thrombin production, but the inflammatory reaction, associated with increased synthesis of alpha1AT, reduced its anticoagulant effect. Lower free plasma APC in CRF may be pathogenically associated with atherothrombosis, a major cause of death in this disease.     

Ethnic differences in the natural progression of nephropathy among diabetes patients in New Zealand: hospital admission rate for renal complications, and incidence of end-stage renal disease and renal death

Aims/hypothesis  We estimated the incidence of chronic renal failure, the incidence of end-stage renal disease (ESRD) and renal mortality rates among New Zealand European and Maori patients with diabetes and estimated the ethnic difference in the risk of developing renal failure. Methods  A renal complication-free cohort of adult diabetes patients registered with Waikato regional diabetes service, diagnosed with diabetes before 2003, were retrospectively followed for 4 years. Events of interest were renal hospital admission, ESRD and death coded with renal disease. Incidences of renal hospital admission, ESRD and death from renal disease were calculated for NZ Europeans and Maori patients with diabetes. Ethnic and sex differences in the risks of these renal outcomes were estimated using a Cox proportional hazards model. Results  Of the 7,900 patients followed up, 116 (1.5%) had a renal admission, 42 (0.5%) started dialysis/transplantation and 21 (0.27%) died from renal disease. Maori diabetes patients had significantly higher incidences of dialysis or transplantation and rates of renal admission and renal death. Adjusted hazard ratios indicate that, compared with NZ Europeans with diabetes, Maori diabetes patients had a significantly higher risk of ESRD, renal admission and renal death (46-fold, seven-fold and four-fold increases, respectively). Maori patients progressed at a significantly faster rate from first hospital admission for chronic renal disease to ESRD. Conclusions/interpretation  There were huge ethnic disparities in outcomes from renal disease. Screening for early kidney disease among Maori diabetes patients, intensive management of risk factors and further research on the aetiology of renal disease among Maoris is recommended.