Statin Intolerance: A Review and Update.

OBJECTIVE: To review the evidence of existing literature on the management of statin intolerance. METHODS: We searched for literature pertaining to statin intolerance and treatments in PubMed. We reviewed articles published between 2005 and 2022. RESULTS: Statin-associated myalgia is the most common adverse effect of statin therapy and the most common reason for statin discontinuation. The risk factors for statin intolerance include unexplained muscle pain with other lipid-lowering therapy, unexplained cramps, a history of increased creatine kinase levels, a family history of muscle symptoms, and a family history of muscle symptoms with lipid therapy. Vitamin D repletion and coenzyme Q supplementation may help alleviate the musculoskeletal effects of statins. Trials of different types of statins and different dosing regimens are recommended to improve tolerability. The use of statins in individuals who perform regular exercise requires closer attention to muscular symptoms and creatine kinase levels; however, it does not preclude the use of statins. CONCLUSION: Management of the adverse effects of statin therapy and improving statin tolerability are key to achieving optimum cardiovascular benefits. Identifying statin-associated adverse effects and managing them appropriately can reduce unnecessary statin discontinuation and subsequently provide longer cardiovascular protection.

Bioenergetics of Islet Preparations in a Pilot Clinical Trial of Peri-Transplant Hydroxychloroquine for Autologous Islet Transplantation.

The inflammatory response is an obstacle to success in both allogeneic and autologous islet transplantation. In autologous islet transplantation (AIT), however, the recipient is also the donor, permitting pretreatment of donor/recipient for a controlled duration prior to transplantation. We sought to exploit this feature of (AIT) by pretreating donor/recipients with chronic pancreatitis undergoing total pancreatectomy and autologous islet transplantation (TPAIT) to test the hypothesis that peri-transplant treatment with the FDA-approved anti-inflammatory hydroxychloroquine (HCQ) improves graft function. In this randomized placebo-controlled pilot clinical study, patients (n = 6) were treated with oral HCQ for 30 days prior to and 90 days after TPAIT. In vivo islet function was assessed via Mixed Meal Tolerance Testing before HCQ treatment, 6- and 12-months after surgery. In vitro islet bioenergetics were assessed at the time of transplantation via extracellular flux analysis of islet preparation samples from the clinical trial cohort and six additional patients (n = 12). Our study shows that HCQ did not alter clinical endpoints, but HCQ-treated patients showed greater spare respiratory capacity (SRC) compared to samples from control patients (P=0.028). Glycolytic metabolism of islet preparations directly correlated with stimulated C-peptide secretion both before and after TPAIT (P=0.01, R2=0.489 and P=0.03, R2=0.674, respectively), and predicted in vivo islet function better than mitochondrial metabolism of islet preps or islet equivalents infused. Overnight culture of islet preparations altered bioenergetic function, significantly decreasing SRC and maximal respiration (P<0.001). In conclusion, while HCQ did not alter clinical outcomes, it was associated with significantly increased SRC in islet preparations. Bioenergetic analyses of islet preparations suggests that culture should be avoided and that glycolysis may be a more sensitive indicator of in vivo islet function than current metrics, including islet oxygen consumption and islet equivalents infused.

Islet Cell Transplantation and Alternative Therapies.

Even though type 2 diabetes rates plateaued, type 1 diabetes continues to increase. Pancreas transplantation is a treatment modality for patients who suffer hypoglycemic unawareness or complications from diabetes. Islet cell transplantation success rates have improved with modification and advances in isolation, transplantation, and new immunosuppression regimens. The new cell sources as well as delivery ways are explored and being tested in human trials.