Diabetes mellitus (DM) can lead to the development of macro- and microvascular complications. Homocysteine (Hcy) may play a role in the development of cardiovascular (CV) diseases (CVDs). The role of Hcy in the development of the vascular complications associated with DM is not clearly defined. Despite a strong initial assumption regarding the importance of Hcy in DM and its complications, over time "enthusiasm has waned" because several studies showed unconvincing and occasionally contradictory results. A universal conclusion is not easy to draw given the diversity of studies (e.g. number of patients, design, folic acid and vitamin B status, ethnic differences, genetic background). For some complications, most results encourages further investigation. Impaired renal function is a major independent determinant of high total Hcy (tHcy) levels. However, the role of hyperhomocysteinaemia (HHcy) in the development of diabetic kidney disease (DKD) has yet to be determined. Hcy-lowering therapies can significantly decrease Hcy levels but their effects on CVD risk reduction are conflicting. Further studies are needed to determine the influence of Hcy-lowering therapy on CVD risk reduction, especially in patients with DM.

High levels of homocysteine (Hcy), known as hyperhomocysteinmia (HHcy), are correlated with an increase in extracellular matrix remodelling (ECM) via the matrix metalloproteinases (MMPs) and plasminogen/plasmin system. This results in an increase deposition of collagen that leads to endothelial-myocyte (EM) and myocyte-myocyte (MM) uncoupling; the physiological consequences are a plethora of cardiovascular pathologies. Homocysteine-induced increase in intracellular and mitochondrial Ca(2+) plays an important role in increasing reactive oxygen species (ROS) within mitochondria and instigating mitophagy within the cell. This occurs via several Hcy-mitigated processes: agonizing N-methyl-d-aspartate receptor-1 (NMDA-R1), decreasing expression of peroxisome proliferator activator receptor (PPAR) [thereby increasing oxidation], impairing Ca(2+) handling via Na(+)/Ca(2+) exchanger (NCX1) and Sarco endoplasmic reticulum Ca(2+) ATPase (SERCA-2a). The end result is an increase in ROS that directly or indirectly lead to MMP activation within mitochondria or the cytoplasm. Hcy induces a mitochondrial permeability transition that allows MMPs to be released from mitochondria thereby metabolizing matrix and impairing cardiac function. Further work remains to be elucidated concerning the specific mitochondrial mitophagic mechanisms under which matrix metabolism and remodelling occurs. Moreover, the therapeutic implications of NMDA and PPAR ligands are some promise to patient.

To determine the incidence and predictors of, and effects of fenofibrate on silent myocardial infarction (MI) in a large contemporary cohort of patients with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

Routine electrocardiograms taken throughout the study were assessed by Minnesota-code criteria for the presence of new Q-waves without clinical presentation and analysed with blinding to treatment allocation and clinical outcome. Of all MIs, 36.8% were silent. Being male, older age, longer diabetes duration, prior cardiovascular disease (CVD), neuropathy, higher HbA(1c), albuminuria, high serum creatinine, and insulin use all significantly predicted risk of clinical or silent MI. Fenofibrate reduced MI (clinical or silent) by 19% [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.94; P = 0.006], non-fatal clinical MI by 24% (P = 0.01), and silent MI by 16% (P = 0.16). Among those having silent MI, fenofibrate reduced subsequent clinical CVD events by 78% (HR 0.22, 95% CI 0.08-0.65; P = 0.003).

Silent and clinical MI have similar risk factors and increase the risk of future CVD events. Fenofibrate reduces the risk of a first MI and substantially reduces the risk of further clinical CVD events after silent MI, supporting its use in type 2 diabetes.

Silent myocardial ischemia (SMI) is a relatively common, yet poorly understood, clinical entity. The most accurate means of detecting SMI and the precise treatment endpoints remain unclear. However, the presence of SMI correlates with the likelihood of future adverse cardiac events. Evidence suggests that patients at high risk of severe cardiac ischemia, even with the absence of symptoms, derive the greatest benefit from an aggressive diagnostic and therapeutic approach. This paper is giving a detailed review of SMI in regards to specific patient subgroups, i.e. populations with diabetes mellitus, hypertension, elderly patients, post-revascularization patients, women, the suggested screening procedures for each subgroup, as well as the emersion of new markers for the selection of high-risk patients for screening.

Fertile chicken eggs were injected with various concentrations of either d-glucose or l-glucose during the first three days of embryonic development. The exogenous glucose concentrations ranged from 0 to 18.58 micromol/kg egg. At 18 days of development (theoretical stage 44), brains, livers, and blood from chorio-allantoic vessels were isolated from living embryos. Exogenous d-glucose and l-glucose caused increased plasma d-glucose levels, increased plasma alanine aminotransferase (ALT) activities, and decreased embryo viability. Embryo viability was monitored by a reduction in the percentage of living embryos at theoretical stage 44, reduced embryo masses, reduced brain masses, and reduced liver masses. When compared to controls, embryonic exposure to either exogenous d-glucose or l-glucose caused increased caspase-3 activities and increased lipid hydroperoxide (LPO) levels in both brain and liver tissues. Because lipid hydroperoxides are lipid peroxidation intermediates that result in the attack of any unsaturated neutral lipid or unsaturated phospholipid, the effect of exogenous glucose on hepatic membrane fatty acid composition was studied. Exogenous glucose (either d-glucose or l-glucose) promoted reduced levels of several unsaturated, long-chain fatty acids and increased levels of saturated, short-chain fatty acids within hepatic membranes. Exogenous-glucose induced decreases in the ratios of unsaturated/saturated fatty acids and long-chain/short-chain fatty acids within hepatic membranes which strongly correlated with glucose-induced increases in plasma ALT activities and moderately correlated to hepatic LPO levels. These observations are consistent with the hypothesis that embryonic hyperglycemia promotes hepatic membrane lipid peroxidation and hepatic cell death.