Is "Leptin Resistance" Another Key Resistance to Manage Type 2 Diabetes?

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

Clinical Use of Marijuana: The Thin Line Between Good and Evil?

From centuries ago cannabis has been known as a botanic product with several properties, with medical use in the ancient world. Nowadays, it is recognized as the active component of marijuana, the drug with the highest rates of illicit use and abuse worldwide according to data provided by the World Health Organization. A huge debate has emerged in these past years with the growing interest to employ cannabis-based products with therapeutic purposes, a strategy that has increased in various European countries, Canada and more than half of the states that conform the United States, simultaneously with an important increase of flexibility in laws and regulations regarding the recreational use of this substance, especially in North America. Although valid arguments can exist for each side, the potential therapeutic use of substances that have ethical-legal implications such as the case of cannabis, require the prescribing doctor to be knowledgeable and to always be updated on the subject, a robust doctor-patient relationship and educational campaigns with truthful information that allow for full awareness of risks vs benefits.