Diabetes mellitus is associated with a considerably increased risk of premature atherosclerotic cardiovascular disease. Intensive glycemic control has essentially failed to significantly improve cardiovascular outcomes in clinical trials. Dyslipidemia is common in diabetes and there is strong evidence that cholesterol lowering improves cardiovascular outcomes, even in patients with apparently unremarkable lipid profiles. Here, the authors review the pathophysiology and implications of the alterations in lipoproteins observed in both type 1 and type 2 diabetes, the effect of medications commonly used in the management of diabetes on the lipid profile, the evidence for lifestyle and pharmaceutical interventions, and national and international recommendations for the management of dyslipidemia in patients with diabetes.

Defects of either anosmin-1 or fibroblast growth factor receptor 1 (FGFR1) are known to underlie hereditary Kallmann's syndrome (KS), a human disorder of olfactory and gonadotropin-releasing hormone (GnRH) neuronal ontogeny. Here, we report a functional interaction between anosmin-1 and the FGFR1-FGF2-heparan sulfate complex, leading to amplified responses in the FGFR1 signaling pathway. In human embryonic GnRH olfactory neuroblasts, wild-type anosmin-1, but not proteins with loss-of-function KS mutations, induces neurite outgrowth and cytoskeletal rearrangements through FGFR1-dependent mechanisms involving p42/44 and p38 mitogen-activated protein kinases and Cdc42/Rac1 activation. Furthermore, anosmin-1 enhances FGF2 signaling specifically through FGFR1 IIIc in heterologous BaF3 lymphoid cells in a heparan sulfate-dependent manner. Our study provides compelling evidence for anosmin-1 as an isoform-specific co-ligand modulator of FGFR signaling that amplifies and specifies FGFR1 signaling responses during human nervous system development and defines a mechanism underlying the link between autosomal and X-linked KS.

High-density lipoprotein (HDL) provides a pathway for the passage of lipid peroxides and lysophospholipids to the liver via hepatic scavenger receptors. Perhaps more importantly, HDL actually metabolizes lipid hydroperoxides preventing their accumulation on low-density lipoprotein (LDL), thus impeding its atherogenic structural modification. A number of candidates have been suggested to be responsible for HDL's antioxidant function, with paraoxonase-1 (PON1) perhaps the most prominent. Here we review the evidence for HDL anti-oxidative function and the potential contributions of apolipoproteins, lipid transfer proteins, paraoxonases and other enzymes associated with HDL.

AimsGuidelines for primary prevention of cardiovascular disease (CVD) with statins, including the most recent, fail to make the best use of the evidence from clinical trials by concentrating on absolute CVD risk as a statin indication and not also considering that a major determinant of therapeutic benefit is the magnitude of the low-density lipoprotein (LDL) (or non-HDL) cholesterol reduction achieved. This decrease is proportional to the pretreatment concentration. We set out to apply this knowledge to the calculation of the number needed to treat to prevent one event (NNT) and to assess critically how current guidelines performed at different degrees of CVD risk across a range of LDL (or non-HDL) cholesterol concentrations. Methods and resultsNumber needed to treat to prevent one event revealed exclusion from the treatment of some people with higher cholesterol levels, who may benefit more than others needlessly exposed to statins with no realistic prospect of benefit. Furthermore, abandonment of cholesterol therapeutic goals disadvantaged people with higher levels. ConclusionThese problems can be overcome by basing the decision to treat on the NNT calculated both from absolute CVD risk and also on the LDL (or non-HDL) cholesterol reduction achievable with statin treatment. This need not adds an additional layer of complexity for the clinician, because computer programmes already used to estimate CVD risk could be easily amended, thus permitting more effective deployment of statins in the population.--