Hyperinsulinemia: A unifying theory of chronic disease?

Globally, there is an increasing prevalence of non-communicable diseases. The morbidity and mortality from these conditions confer a greater economic societal burden. Epidemiological research associates insulin resistance in the etiology of these diseases, but there is limited evidence for the mechanism of damage. Emerging research suggests that hyperinsulinemia, a symptom of insulin resistance, may cause these pathological changes, and therefore be an independent contributor to these diseases. This review shows that hyperinsulinemia, or excessive insulin secretion, should be considered independently to insulin resistance, defined as glucose uptake rate, even though the two conditions are intertwined and will co-exist under normal conditions. Hyperinsulinemia directly and indirectly contributes to a vast array of metabolic diseases including all inflammatory conditions, all vascular diseases, gestational and type 2 diabetes, non-alcoholic fatty liver disease, obesity and certain cancers and dementias. The mechanisms include increased production of: insulin growth factor-1; reactive oxidative species and advanced glycation end-products; and triglyceride and fatty acids. Hyperinsulinemia also directly and indirectly affects many other hormones and cytokine mechanisms including leptin, adiponectin and estrogen. There is limited research standardizing the hyperinsulinemia diagnostic process. Methodological concerns and lack of standardized reference ranges preclude the use of fasting insulin. Most research has also focused on insulin resistance and it is unknown whether these methods translate to hyperinsulinemia

Lorcaserin: Making headway

Obesity is a global problem which has reached epidemic proportions. Obesity is morbidly associated with metabolic syndrome, type-2 diabetes, cardiovascular disease and increased cancer risk. There is an alarming increase in the incidence of obesity in young children which puts them at a greater risk for developing diseases at a much earlier age. Obesity also imposes a heavy burden on the healthcare system. Lorcaserin, a novel anti-obesity drug, is a selective agonist to 5-HT2C receptors thereby reducing food intake and promoting weight loss. Lorcaserin has 15-times and 100-times higher selectivity for the 5-HT2C receptor compared to the 5-HT2A and 5-HT2B receptors, respectivel

Errata: Hyperinsulinemia: A unifying theory of chronic disease?

Errata: The original article was published with an error of hyperinsulinemia improves fibrinolysis, instead hyperinsulinemia impairs fibrinolysis. The error has been corrected in this version

Canagliflozin in the treatment of diabetes: Perspectives

The worldwide prevalence of type 2 diabetes mellitus (T2DM) has surpassed more than 380 million people in 2014 and the projections of new T2DM cases for the next years are not encouraging. At present, combination of diet and exercise do not guarantee an adequate control of glucose homeostasis in T2DM patients. Thus, oral agents that act improving peripheral insulin sensitivity and/or pancreatic beta-cell function are additionally used as monotherapy or in combination. However, many patients still experience inadequate control with the pharmacotherapy ‘weapons’ currently available. Canagliflozin is a novel selective inhibitor of sodium-glucose co-transporter 2 (SGLT2) that lowers blood glucose concentration mainly by augmenting urinary glucose excretion. Besides having an effective action in reducing HbA1c, canagliflozin treatment also may benefit those patients aiming to control body weight, blood pressure and hypoglycemia episodes since this drug positively impact on such parameters. Among the adverse effects, genital infections are the most frequent. Much caution is required for some groups of patients including those elderly and with chronic kidney disease since canagliflozin can worse their quality of life. Given its overall cardiometabolic improvements, canagliflozin seems to be an important ally to the treatment of a selective group of T2DM patients and its efficacy and safety must be kept under monitoring through long-term clinical trials as well as experimental studies to certify whether this class of drug comes to stay among T2DM therapy