The Ketogenic Effect of SGLT-2 Inhibitors-Beneficial or Harmful?

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, also called gliflozins or flozins, are a class of drugs that have been increasingly used in the management of type 2 diabetes mellitus (T2DM) due to their glucose-lowering, cardiovascular (CV), and renal positive effects. However, recent studies suggest that SGLT-2 inhibitors might also have a ketogenic effect, increasing ketone body production. While this can be beneficial for some patients, it may also result in several potential unfavorable effects, such as decreased bone mineral density, infections, and ketoacidosis, among others. Due to the intricate and multifaceted impact caused by SGLT-2 inhibitors, this initially anti-diabetic class of medications has been effectively used to treat both patients with chronic kidney disease (CKD) and those with heart failure (HF). Additionally, their therapeutic potential appears to extend beyond the currently investigated conditions. The objective of this review article is to present a thorough summary of the latest research on the mechanism of action of SGLT-2 inhibitors, their ketogenesis, and their potential synergy with the ketogenic diet for managing diabetes. The article particularly discusses the benefits and risks of combining SGLT-2 inhibitors with the ketogenic diet and their clinical applications and compares them with other anti-diabetic agents in terms of ketogenic effects. It also explores future directions regarding the ketogenic effects of SGLT-2 inhibitors.

Del Nido cardioplegia as a safe and effective method of myocardial protection in adult patients undergoing cardiac surgery: a single­center experience.

BACKGROUND: Del Nido (DN) cardioplegia is increasingly popular in adult cardiac surgery. It allegedly allows for up to 90 minutes of safe myocardial ischemia with a single dose. AIMS: We aimed to evaluate the benefits of DN cardioplegia. METHODS: Of the 2108 patients undergoing coronary or heart valve surgery with the use of cardiopulmonary bypass (CPB) between January 1, 2016, and September 30, 2017, 1236 (59%) received DN and 872 (41%) received cold blood cardioplegia. We retrospectively analyzed the collected data of all consecutive on­pump patients to assess early mortality and postoperative troponin T release. A multivariable analysis of both outcomes adjusted for propensity to receive DN cardioplegia was performed. RESULTS: Patients protected with DN cardioplegia had longer CPB and aortic cross­clamp times (P <0.001) but received fewer doses of cardioplegia. Median postoperative troponin T levels were higher in the DN­cardioplegia than CB­cardioplegia group: 0.324 ng/ml (interquartile range [IQR], 0.210-0.559 ng/ml) vs 0.285 ng/ml (IQR, 0.191-0.496 ng/ml); P = 0.01. However, when adjusted for the cross­clamp time, propensity to receive DN cardioplegia, and other factors, DN cardioplegia was associated with lower postoperative troponin T levels. Early mortality rates did not differ between DN and CB cardioplegia (3.6% vs 3%; P = 0.54). CONCLUSIONS: Del Nido cardioplegia is a safe and effective method of myocardial protection in adults. It allows for a longer redosing interval with a safety profile and mortality comparable to those for CB cardioplegia, as shown by lower troponin T release when corrected for the time of myocardial ischemia.