Do statins cause diabetes?

A wealth of evidence has established that cholesterol-lowering statin drugs, widely used for the prevention of cardiovascular disease, do increase the risk of new-onset diabetes, possibly by impairing pancreatic beta cell function and decreasing peripheral insulin sensitivity. Groups at particular risk include the elderly, women, and Asians. The diabetogenic effect of statins appear directly related to statin dose and the degree of attained cholesterol lowering. Statins can cause hyperinsulinemia even in the absence of hyperglycemia and the potential mitogenic effects and implications of prolonged hyperinsulinemia are discussed. Suggestions are made as to how physicians might avert the hyperinsulinemic and diabetogenic effects of statin therapy in clinical practice, and modulate the detrimental effects of these drugs on exercise performance. Finally, long-term studies are needed to determine if the deleterious hyperinsulinemic and diabetogenic effects of statin therapy undermine the beneficial cardiovascular disease risk outcomes in various segments of the population.

On the prevention and treatment of Alzheimer's disease: Control the promoters and look beyond the brain.

Alzheimer's disease (AD) is a progressive incurable neurodegenerative disease of the brain afflicting a third of the population aged 85 and older. Pathologic hallmarks include extracellular plaques of amyloid-beta (Aß), intraneuronal neurofibrillary tangles of hyperphosphorylated tau protein, synaptic destruction, neuronal death, and brain atrophy. Neuroinflammation, mediated by microglia, is a central component of the disease, and is intricately connected with peripheral inflammation. The clinical manifestations include progressive memory loss and eventual death. The present treatment of AD is largely ineffective. Nearly all AD is late-onset and presents age 65 or older, and the most common genetic risk factor is carriage of an apolipoprotein (APO) E4 allele, seen in about 25% of the general population. Individuals carrying an APOE4 allele produce more Aß and clear it less efficiently from the brain throughout life. There has been accumulating pathologic and clinical evidence that microbes, particularly the herpes simplex virus (HSV), is a causative factor for AD, most notable in carriers of the APOE4 allele. Eighty percent of the adult population harbors HSV and it resides in the trigeminal ganglion in latent state throughout life, but periodically reactivates, traveling antegrade resulting in herpes labialis and traveling retrograde into the brain leading to neuroinflammation. Functioning as an antimicrobial peptide, Aß inactivates HSV and the recurring process culminates in a buildup of Aß plaque and other hallmarks of AD over time. Periodontal disease exists in 20-50% of the adult population and is also a causative factor for AD. Accordingly, bacteria causing periodontal disease and their byproducts can enter the brain directly via the trigeminal nerve or indirectly through the bloodstream, resulting in AD pathology over time. There are many other promoters of AD, particularly inflammatory conditions outside of the brain, that can be mitigated. Small trials are finally in progress testing antimicrobial drugs for the prevention and treatment of AD. In the meantime, a more proactive approach to the prevention and treatment of AD is posited, with an emphasis on prevention, since the pathologic underpinnings of the disease start decades before the clinical manifestations. Individuals can be stratified in risk categories using family history, periodontal disease presence, APOE4 carriage, and HSV IgG positivity. Moderate- and high-risk individuals can be treated safely with various preventive measures and appropriate antimicrobial agents as discussed. Importantly, the proposed treatments are concordant with the accepted practice of medicine, and if utilized, could significantly decrease AD prevalence.

[Vitamin D deficiency and cardiovascular diseases]. / Carenza di vitamina D e malattie cardiovascolari.

The increasing worldwide displacement from the natural outdoor environment of human beings to an indoor sedentary lifestyle, along with the recommendation to avoid any direct sun exposure because of the risk of skin cancer, has resulted in a global pandemic of vitamin D insufficiency. Traditionally, vitamin D has been associated primarily with bone health. However, it has become evident that adequate vitamin D status is important for optimal function of many organs and tissues throughout the body, including the cardiovascular system. Vitamin D insufficiency seems to predispose to hypertension, diabetes and the metabolic syndrome, left ventricular hypertrophy, heart failure, and chronic vascular inflammation. The relationship between baseline vitamin D status, dose of vitamin D supplements, and cardiovascular events remains to be investigated by ongoing randomized trials; however increasing evidence suggests that the provision of a simple, well-tolerated, and inexpensive correction of vitamin D insufficiency favourably affects the morbility and mortality of cardiovascular disease along with the prevention of the most common chronic degenerative diseases.