Determinants of urinary albumin excretion within the normal range in patients with type 2 diabetes: the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study

In contrast to microalbuminuric type 2 diabetic patients, the factors correlated with urinary albumin excretion are less well known in normoalbuminuric patients. This may be important because even within the normoalbuminuric range, higher rates of albuminuria are known to be associated with higher renal and cardiovascular risk. At the time of screening for the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) Study, the urinary albumin/creatinine ratio (UACR) was 0.44 mg/mmol in 4,449 type 2 diabetic patients. The independent correlates of UACR were analysed. Independent correlates of UACR during baseline were (in descending order): night-time systolic BP (r (s) = 0.19); HbA(1c) (r (s) = 0.18); mean 24 h systolic BP (r (s) = 0.16); fasting blood glucose (r (s) = 0.16); night-time diastolic BP (r (s) = 0.12); office systolic BP, sitting (r (s) = 0.11), standing (r (s) = 0.10); estimated GFR (r (s) = 0.10); heart rate, sitting (r (s) = 0.10); haemoglobin (r (s) = -0.10); triacylglycerol (r (s) = 0.09); and uric acid (r (s) = -0.08; all p a parts per thousand currency signaEuro parts per thousand 0.001). Significantly higher albumin excretion rates were found for the following categorical variables: higher waist circumference (more marked in men); presence of the metabolic syndrome; smoking (difference more marked in males); female sex; antihypertensive treatment; use of amlodipine; insulin treatment; family history of diabetes; and family history of cardiovascular disease (more marked in women). Although observational correlations do not prove causality, in normoalbuminuric type 2 diabetic patients the albumin excretion rate is correlated with many factors that are potentially susceptible to intervention. ClinicalTrials.gov ID no.: NCT00185159 This study was sponsored by Daichii-Sankyo.Nephrolog

From reaching every district to reaching every community: analysis and response to the challenge of equity in immunization in Cambodia

BACKGROUND An international review of the Cambodian Expanded Programme on Immunization (EPI) in 2010 and other data show that despite immunization coverage increases and vaccine preventable diseases incidence reductions, inequities in access to immunization services exist. Utilizing immunization and health systems literature, analysis of global health databases and the EPI review findings, this paper examines the characteristics of immunization access and outcome inequities, and describes proposed longer-term strategic and operational responses to these problems. Findings The national programme has evolved from earlier central and provincial level planning to strengthening routine immunization coverage through the District level 'Reaching Every District Strategy'. However, despite remarkable improvements, the review found over 20% of children surveyed were not fully immunized, primarily from communities where inequities of both access and impact persist. These inequities relate mainly to socio-economic exposures including wealth and education level, population mobility and ethnicity. To address these problems, a shift in strategic and operational response is proposed that will include (a) a re-focus of planning on facility level to detect disadvantaged communities, (b) establishment of monitoring systems to provide detailed information on community access and utilization, (c) development of communication strategies and health networks that enable providers to adjust service delivery according to the needs of vulnerable populations, and (d) securing financial, management and political commitment for 'reaching every community'. CONCLUSIONS For Cambodia to achieve its immunization equity objectives and disease reduction goals, a shift of emphasis to health centre and community is needed. This approach will maximize the benefits of new vaccine introduction in the coming 'Decade of Vaccines', plus potentially extend the reach of other life-saving maternal and child health interventions to the socially disadvantaged, both in Cambodia and in other countries with a similar level of development

PPAR alpha: an emerging therapeutic target in diabetic microvascular damage

The global pandemic of diabetes mellitus portends an alarming rise in the prevalence of microvascular complications, despite advanced therapies for hyperglycemia, hypertension and dyslipidemia. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is expressed in organs affected by diabetic microvascular disease (retina, kidney and nerves), and its expression is regulated specifically in these tissues. Experimental evidence suggests that PPAR alpha activation attenuates or inhibits several mediators of vascular damage, including lipotoxicity, inflammation, reactive oxygen species generation, endothelial dysfunction, angiogenesis and thrombosis, and thus might influence intracellular signaling pathways that lead to microvascular complications. PPAR alpha has emerged as a novel target to prevent microvascular disease, via both its lipid-related and lipid-unrelated actions. Despite strong experimental evidence of the potential benefits of PPAR alpha agonists in the prevention of vascular damage, the evidence from clinical studies in patients with diabetes mellitus remains limited. Promising findings from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study on microvascular outcomes are countered by elevations in participants' homocysteine and creatinine levels that might potentially attenuate the benefits of PPAR alpha activation. This Review focuses on the role of PPAR alpha activation in diabetic microvascular disease and highlights the available experimental and clinical evidence from studies of PPAR alpha agonists