Statin-Induced Diabetes Demands a more Personalized Approach

Updated: May 16

Disclaimer: This article is written to serve as a source of perspective based on my view and the existing scientific evidence. On no account should it be used as medical advice. My advice is for everyone to consult their medical doctor to seek the unsurpassed personalized treatment option.

Originally Published by Illumination Curated on Medium

Photo by Olga DeLawrence on Unsplash

Recently, I published a couple of articles focusing on statin cholesterol-lowering agents’ potential benefits and untoward side effects.

Statins are the layperson name given to HMG-CoA reductase inhibitors, such as Atorvastatin, Rosuvastatin, Simvastatin, Cholesterol, Fibrate, Ezetimibe, Pravastatin, and more. They are a class of lipid-lowering medications that reduce illness and mortality in those at high risk of cardiovascular disease. Today, Statins are among the utmost used drugs to avert unfavorable cardiovascular incidents.

Unfortunately, statins received a US Food and Drug Administration alert in 2012, scrutinizing the increased risk of incident diabetes and making blood glucose control even harder in patients who already have diabetes. It is also speculated; that statins of the various families differ concerning their diabetes causing potential. Since there is also an increased association between diabetes and cardiovascular disease (CVD) and elevated cholesterol, drawing the clinical decision line as to whom to treat with statins today is an intricate decision.

Presently multiple clinical reviews are trying to fine-tune the clinical decision on statin therapy.

Evidence pointing toward the Diabetogenic effect of the Statins

Diabetes causing effect of statins didn’t recurve much attention until 2008, of results of the Intervention Trial Evaluating Rosuvastatin (JUPITER), were conducted and reported. The latter was a large, randomized, placebo-controlled, primary prevention trial. The study revealed an increased incidence of diabetes in persons taking rosuvastatin (a type of Satin) was reported in this trial,

Previous to the JUPITER study, the West of Scotland Coronary Prevention Study (WOSCOP) study (2001) reported a 30% risk reduction for diabetes with pravastatin. But conversely, the study found a 32% higher incidence of diabetes with pravastatin therapy for the elderly. Furthermore, long-term Pravastatin therapy observation naked no reduction in the incidence of diabetes in the long-term intervention with pravastatin in the ischemic disease trial.

There have been at least another three studies with various sets of outcomes regarding linking statins with diabetes.

A Statin therapy meta-analysis of five studies demonstrates a 13% increase in diabetes risk with no array across trials. However, the analysis also concludes; that when data from WOSCOP was incorporated, the danger became statistically trivial. Then again, another meta-analysis by Sattar et al. included 13 randomized placebo-controlled and standard care-controlled trials with 91,140 participants. The study indicated a 9% expanded risk of diabetes incidence with little heterogeneity between trials.

Another study carried out by Preiss et al. in 2011 confirms that a higher statin dosage carries a higher diabetogenic effect with a 12% higher risk on intensive-dose statin therapy than moderate-dose treatment.

Statins may potentially affect Blood Glucose Homeostasis

Some studies substantiate the theory that statins may modify glucose homeostasis by both impairing insulin secretion and diminished insulin sensitivity of the cells. Possibly statin induces diabetes. Amid the cholesterol synthesis process (from acetyl CoA), numerous byproducts such as Isoprenoid, Farnesyl pyrophosphate, Geranylgeranyl pyrophosphate, and Ubiquinone (Coenzyme Q10 [CoQ10]) are affected. The latter, in turn, tend to hinder insulin secretion or action. For instance, statins are known to deplete CoQ10 levels, which is a component of the biochemical chain of development involved in the process of ATP (a cell energy factor) generation. Curtailed levels of CoQ10 can result in delayed production of ATP and consequently diminish insulin release.

Furthermore, statins down-regulate a factor called GLUT4 in fat cells. GLUT4 mediates insulin-stimulated glucose uptake by skeletal muscles and adipocytes. Atorvastatin and Simvastatin have been shown to decrease the expression of GLUT4 in adipocytes which may result in impaired glucose tolerance.

Adiponectin is an insulin-sensitizing and anti-inflammatory cytokine typically released from fat cells. Rosuvastatin and Simvastatin have decreased plasma adiponectin levels and insulin sensitivity, while pravastatin increased both.

Statins may also cause Mitochondrial dysfunction in cells that produce insulin (beta cells of the pancreas), skeletal muscles, and fat cells. In addition, statin-induced myalgia and fatigue may impair exercise capacity and aggravate sarcopenia, associated with glucose intolerance and type 2 diabetes.

Some Statins may be better than others

There are generally two chemical forms of statins; fat-soluble (lipophilic) and water-soluble (Hydrophilic) Statins.

Statin medications: Atorvastatin, Simvastatin, lovastatin, Fluvastatin, and Pitavastatin are relatively lipophilic in chemical structure, while pravastatin and rosuvastatin are relatively hydrophilic.

It has been deduced that lipophilic statins are probably more diabetes-causing. Because they readily penetrate liver cell membranes such as beta cells, adipocytes, and skeletal muscles.

Therapy with Statin Drugs necessitates a personalized Approach

For many reasons Association of statin use with new-onset diabetes presents a predicament for the physician.

  1. diabetes is equivalent to coronary heart disease risk

  2. High cholesterol level is a distinct feature of diabetes

  3. persons at risk for CVD (including persons with Dyslipidemia) may be prediabetic and finally

  4. risk factors for diabetes and CVD are overlapping.

It seems that treatment with statins may metaphorically be a double-edged sword as it is hard to delineate when to Prescribe only when indicated clearly. Reports suggest that statins are prescribed liberally when used when there is a clear therapeutic rationale. However, that justification will never come to us if we continue the path of statistics.

True, it is always logical if we Start with low doses to reduce higher risk. Likewise, High dose statins are better averted in women and the elderly. Also, water-soluble ones may be better all with lifestyle modification

The benefits of regular exercise and dietary changes should be stressed at every contact with the patient.