Statins: Sugar-Coating the Effects

Statins. They’re as controversial a topic as cholesterol itself. Medical professionals have a love-hate relationship with these drugs, with some regarding them as lifesaving pharmaceutical miracles, and others claiming they represent all that is wrong with modern medicine. Yet, as with all compounds that significantly alter a complex biochemical pathway, statins bring unintended consequences.

There is a growing awareness that statin drug use may be associated with an increased risk for type 2 diabetes. Although the risk may be small, it is significant enough for the FDA to acknowledge that statins may result in elevated blood glucose and hemoglobin A1cstatins, thus conferring an increased risk for type 2 diabetes. The highly respected Mayo Clinic also lists increased blood sugar  among the potential side-effects of statins.

A recent study added more fuel to the fire when the results indicated a clinically significant increase in new diabetes diagnosis among men ages 43-75 who were taking statin drugs. Compared to subjects not taking statins, those receiving statin therapy had a 46% increased risk for type 2 diabetes during the 6-year follow-up, with the risk specified as dose-dependent for those taking simvastatin and atorvastatin. Among the men receiving statin treatment, insulin sensitivity was decreased by 24% and insulin secretion by 12% compared to individuals not being treated with statins, with these effects also being dose-dependent for simvastatin and atorvastatin.

Out of a total of 8,749 subjects, 625 received new diagnoses of type 2 diabetes. However, compared to subjects who remained healthy, those who became diabetic were older, more obese, less physically active, had lower HDL levels, higher fasting blood glucose and HbA1c, and higher triglycerides. So these subjects had greater risk factors for developing type 2 diabetes and metabolic syndrome regardless of whether they were taking a statin or not. This doesn’t negate a potential role for statins in contributing even further to the risk for diabetes, but it’s important to note that these subjects were already at a higher risk.

While a drug intended to lower serum cholesterol levels may seem unrelated to blood glucose regulation, there is, in fact, a biochemical mechanism by which statins may affect pancreatic beta cell function. Statin is a generic name for drugs that inhibit HMG CoA reductase, a key enzyme in the mevalonate pathway. By inhibiting this enzyme, statins do, indeed, reduce the endogenous synthesis of cholesterol. But they also decrease synthesis of many other substances that are produced along the same pathway.

Among these crucial substances are prenylated proteins, formed from farnesyl pyrophosphate and geranylgeranyl pyrophosphate building blocks. These little-known compounds are required for glucose stimulated secretion of insulin. Disruption in synthesis of the precursor molecule, mevalonic acid, by HMG CoA reductase inhibitors, has been shown to inhibit glucose-stimulated insulin secretion from normal rat islet cells. According to one researcher,  “Inhibition of protein prenylation in β-cells results in selective accumulation of unprenylated G proteins…possibly interfering with the interaction of these proteins with their respective effector proteins, which may be required for nutrient-induced insulin secretion.” Other studies support these findings—that inhibition of protein prenylation/isoprenylation (specifically by lovastatin) may adversely affect the ability of the pancreas to secrete insulin in response to rising blood glucose.

The mechanism by which this might occur is that prenylation/isoprenylation seems to be required for intracellular trans location of the “G” proteins involved in the B-cell function. . There might even be a role for protein prenylation in protecting against the death of β-cells, which results in type 1 diabetes. According to researchers, “These post translational modification steps not only play obligatory roles in fuel-induced insulin secretion, but also in cytokine-mediated apoptotic demise of the beta cell.”

As we know, the use of statin drugs is riddled with controversy. The use of total cholesterol levels or even just LDL-cholesterol levels as markers for heart disease risk has been called into question. Amidst this controversy, statins do seem to get the nod for reducing risk for a coronary event in patients with existing coronary disease or at high risk,, as well as those who have already experienced a coronary event (secondary prevention). Some researchers have called for statin prescribing guidelines to be more precisely defined by parameters of gender and age, suggesting that when it comes to treating risk factors for coronary and cardiovascular events, there is no”one size fits all” approach. The use of statin drugs to reduce bio markers associated with heart disease should be weighed against the potential development of other conditions that may lead to increased morbidity and mortality, however unintended these consequences may be.

I have an entire library of information regarding the dangers of statins.
Keep in mind high cholesterol is not a result of low stain levels in the blood