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Studies that investigate use of diabetes technologies such as blood glucose monitoring (BGM) and continuous glucose monitoring (CGM) often report contradictory findings regarding efficacy and clinical utility. Whereas some studies of a given technology have shown no benefit, others have reported significant benefits. These incongruities derive from how the technology is viewed. Is it viewed as a tool, or is it an intervention? In this article, we discuss earlier studies that illustrate the contrast between use of BGM as a tool versus use as an intervention, compare and contrast the roles of BGM and CGM as tools and/or interventions in diabetes management, and suggest that CGM can function effectively as both. [ABSTRACT FROM AUTHOR]

HDL from healthy humans and lean mice inhibits palmltate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgN[O.sub.3] fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgN[O.sub.3]- injected mice lacking Saa1.1 and Saa2.1 exhibited a partial restoration of antiinflammatory and cholesterol efflux properties in adipocytes. Conversely, incorporation of SAA into HDL preparations reduced antiinflammatory properties but not to the same extent as HDL from AgN[O.sub.3]-injected mice. SAA-enriched HDL colocalized with cell surface-associated extracellular matrix (ECM) of adipocytes, suggesting impaired access to the plasma membrane. Enzymatic digestion of proteoglycans in the ECM restored the ability of SAA-containing HDL to inhibit palmitate-induced inflammation and cholesterol efflux. Collectively, these findings indicate that inflammation results in a loss of the antiinflammatory properties of HDL on adipocytes, which appears to partially result from the SAA component of HDL binding to cell-surface proteoglycans, thereby preventing access of HDL to the plasma membrane., Introduction HDL-cholesterol levels are reduced in obesity, especially in those individuals with features of the metabolic syndrome (1, 2). The metabolic syndrome is accompanied by adipose tissue (AT) (3, 4) [...]

Fibrates, activators of the nuclear receptor PPAR[alpha], improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPAR[alpha] activation improves insulin resistance and vascular function, we determined the effects of fenofibrate in healthy adults with insulin resistance induced by short-term glucocorticoid administration. Eighteen normal-weight subjects were studied in four stages: at baseline, after 21 days of fenofibrate (160 mg/day) alone, after 3 days of dexamethasone (8 mg/day) added to fenofibrate, and after 3 days of dexamethasone added to placebo (dexamethasone alone). Dexamethasone alone caused hyperinsulinemia, increased glucose, decreased glucose disposal, and reduced insulin-induced suppression of hepatic glucose production as determined by hyperinsulinemic euglycemic clamp and increased systolic blood pressure as determined by ambulatory monitoring, features associated with an insulin-resistant state. Fenofibrate improved fasting LDL and total cholesterol in the setting of dexamethasone treatment but had no significant effect on levels of insulin or glucose, insulin-stimulated glucose disposal, or insulin suppression of glucose production during clamps, or ambulatory monitored blood pressure. In the absence of dexamethasone, fenofibrate lowered fasting triglycerides and cholesterol but unexpectedly increased systolic blood pressure by ambulatory monitoring. These data suggest that PPAR[alpha] activation in humans does not correct insulin resistance induced by glucocorticoids and may adversely affect blood pressure. peroxisome proliferator-activated receptor-[alpha]; dexamethasone; insulin sensitivity; metabolic syndrome

Abstract Background There is widespread agreement on the need for scaling up in the health sector to achieve the Millennium Development Goals (MDGs). But many countries are not on track to reach the MDG targets. The dominant approach used by global health initiatives promotes uniform interventions and targets, assuming that specific technical interventions tested in one country can be replicated across countries to rapidly expand coverage. Yet countries scale up health services and progress against the MDGs at very different rates. Global health initiatives need to take advantage of what has been learned about scaling up. Methods A systematic literature review was conducted to identify conceptual models for scaling up health in developing countries, with the articles assessed according to the practical concerns of how to scale up, including the planning, monitoring and implementation approaches. Results We identified six conceptual models for scaling up in health based on experience with expanding pilot projects and diffusion of innovations. They place importance on paying attention to enhancing organizational, functional, and political capabilities through experimentation and adaptation of strategies in addition to increasing the coverage and range of health services. These scaling up approaches focus on fostering sustainable institutions and the constructive engagement between end users and the provider and financing organizations. Conclusions The current approaches to scaling up health services to reach the MDGs are overly simplistic and not working adequately. Rather than relying on blueprint planning and raising funds, an approach characteristic of current global health efforts, experience with alternative models suggests that more promising pathways involve "learning by doing" in ways that engage key stakeholders, uses data to address constraints, and incorporates results from pilot projects. Such approaches should be applied to current strategies to achieve the MDGs.

Obesity is a chronic inflammatory state characterized by altered levels of adipose tissue immune cell populations. Natural killer T (NKT) cells are CD1d restricted lymphocyte subsets that recognize lipid antigens whose level decreases in obese adipose tissue. However, studies in mice with deficiency or increased levels of NKT cells have yielded contradictory results, so the exact role of these cells in obesity and adipose tissue inflammation is not yet established. We previously showed that Ldlr−/− mice with excess invariant NKT (iNKT) cells demonstrate significant weight gain, adiposity, metabolic abnormalities, and atherosclerosis. The current study evaluates the effects of NKT cell deficiency on obesity, associated metabolic changes, and atherosclerosis in Jα18−/−Ldlr−/− (lacking iNKT cells) and Cd1d−/−Ldlr−/− (lacking invariant and type II NKT cells) mice, and control mice were fed an obesogenic diet (high fat, sucrose, cholesterol) for 16 weeks. Contrary to expectations, Ja18−/−Ldlr−/− mice gained significantly more weight than Ldlr−/− or Cd1d−/−Ldlr−/− mice, developed hypertriglyceridemia, and had worsened adipose tissue inflammation. All the mice developed insulin resistance and hepatic triglyceride accumulation. Ja18−/−Ldlr−/− mice also had increased atherosclerotic lesion area. Our findings suggest that iNKT cells exacerbates the metabolic, inflammatory, and atherosclerotic features of diet-induced obesity. Further work is required to unravel the paradox of an apparently similar effect of iNKT cell surplus and depletion on obesity. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. A "two-hit" hypothesis has been proposed for progression of a normal healthy liver to steatohepatitis (NASH), involving first the development of obesity and insulin resistance (IR) followed by hepatic inflammation. Most studies of NAFLD and NASH in mice have used a methionine/choline deficient diet or genetically modified models. However, the histology does not closely resemble human NAFLD. The LDL receptor-deficient mouse (LDLR-/-) is a model traditionally used for studying atherosclerosis, but develops hepatic steatosis on a high fat Western-type diet. To study the effects of diet-induced obesity and IR on the liver, we compared LDLR-/- mice fed a diabetogenic (high fat, high carbohydrate) diet, without or with added cholesterol (0.15%w/w; DD-C and DD+C respectively) vs chow-fed controls. Mice fed both diabetogenic diets developed IR and obesity. ALT levels were 4- and 5-fold higher in DD-C and DD+C than in controls (44±5; 173±30; 212±43 U/L, p<0.001). Hepatic triglyceride content was high in DD-C and further increased in DD+C (p=0.002). Parallel elevations in circulating FFA levels were noted (0.34±0.05; 1.33±0.27; 2.0±0.36 mmol/L, p<0.0001). Circulating serum amyloid A (SAA) and hepatic SAA mRNA were elevated in DD-C and highest in the DD+C, suggestive of chronic inflammation. Hepatic TNFα mRNA levels were 2- and 2.5-fold higher in the DD-C and DD+C groups compared to controls. Plasma ALT levels were strongly correlated with plasma insulin levels (r²= 0.70, p<0.0001) as well as the extent of atherosclerosis (r²=0.52, p=0.005). Liver histology showed diffuse macrovesicular steatosis in a non-zonal pattern in DD-C. By contrast, liver histology in DD+C showed both macro- and microvesicular steatosis with a predominant centrilobular distribution. Features associated with NASH (intrasinusoidal and pericellular fibrosis) also were seen in both groups. Thus, consumption of a high fat, high carbohydrate diet results in phenotypic changes (obesity, IR and systemic inflammation) associated with the metabolic syndrome, together with histologic features of NAFLD. Dietary cholesterol results in a distinct hepatic phenotype characterized by increased microvesicular steatosis and a centrilobular pattern of fat deposition. Therefore, LDLR-/- mice fed diets high in fat and carbohydrate without or with cholesterol may represent variant models for studying the pathophysiology of human NASH. [ABSTRACT FROM AUTHOR]