Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

These studies were conducted to determine whether there are gender-specific regional differences in meal triglyceride fatty acid uptake. Systemic and regional oleate ([3H]oleate) kinetics were measured in nine nonobese men and eight nonobese women before and at the end of a 6-h meal, administered as small frequent feedings to achieve steady-state chylomicronemia. Chylomicron uptake in the splanchnic bed accounted for 71 +/- 15% of meal triglyceride disappearance in men and 20 +/- 7% in women (P < 0.01), whereas leg chylomicron uptake could only account for 12 +/- 2 and 8 +/- 4% (P not significant in men vs. women) of meal triglyceride disappearance. Meal ingestion suppressed (P < 0.05) systemic and regional free fatty acid release in both men and women. Splanchnic nonchylomicron triglyceride release and leg nonchylomicron triglyceride uptake were not significantly different in men and women. In summary, the largest quantitative difference between men and women in fatty acid kinetics during meal ingestion is a substantially greater splanchnic uptake of meal triglyceride fatty acids in men. This could represent greater meal fatty acid storage in visceral adipose tissue.

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Hyperhomocysteinemia (HH) and metabolic syndrome (MS) are associated with increased cardiovascular risk. However, whether there is a link between MS or its components and homocysteine levels in a population without cardiovascular disease is not well established. We conducted a case-control study in 61 MS patients (41 males, 20 females, aged 51 ± 11 years) and in 98 controls without MS (59 males, 39 females, aged 50 ± 10 years) to ascertain the association between MS and HH, and with inflammatory markers. MS was classified according to the updated ATPIII criteria [17]. No differences in homocysteine levels were observed when comparing MS patients and controls (12.0 ± 3.18 M vs. 11.9 ± 3.5 M, p = 0.829). No association was found between HH (homocysteine >15 M) and MS, its components (abdominal obesity (p = 0.635), hypertension (0.229), low-HDL cholesterol (p = 0.491), glucose >100 mg/dL (0.485), hypertriglyceridemia (p = 0.490)) or the number of MS components (p = 272). When considering glucose >110 mg/dL (NCEP-ATPIII criteria, 2001) instead of glucose intolerancen >100 mg/dl (updated ATPIII criteria, Grundy, 2005), a borderline association with HH was observed (p = 0.054) of statistical significance (p = 0.008) when glucose >126 mg/dL was considered. In a multivariate regression model, creatinine, folic acid and vitamin B12 were the only independent predictors of homocysteine levels (p < 0.05).Although MS correlated with inflammatory parameters (fibrinogen, hs-RCP, plasma viscosity and leukocyte count, p < 0.001), no association was found between HH and the above-mentioned parameters (p > 0.05).Our results do not indicate a link between SM or its individual components with HH, and diabetes was the only relevant contribution. Cardiovascular disease risk due to MS and HH seems to share no common mechanisms.

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.