Lege Artis Medicinae

[The development of insulin treatment from discovery of insulin to analogue preparations]

KÁPLÁR Miklós, PARAGH György

SEPTEMBER 20, 2011

Lege Artis Medicinae - 2011;21(08-09)

[The discovery of insulin was a milestone in the treatment of diabetes mellitus. Animalderived (porcine and cattle) insulins available at the beginning were later replaced by human insulins. Recently, analogue insulins are the most widespreadly used. Besides the increase in the quantity and improvement in the quality of the insulin products, the growth of the treatment regimes is apparent, as well. That varies from the once-given daily basal insulin treatment added to oral antidiabetic drugs to intensified insulin therapy, administering insulin 4-5 times daily. Considering the benefits proved by previous basic and clinical studies, the authors summarize the most important properties of the commonly used insulin treatment regimes in this review. They also briefly outline the important aspects of the patient-centered personalized therapy and the connection between insulin therapy and carcinogenesis.]

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[The primary goals of the treatment of AMI are to rapidly open - either mechanically or by thrombolysis - the blocked blood vessel and to keep it open. Restarting of the blood flow in blocked vessels results in an increased load in volume, pressure and metabolism in the blood vessel's supply area, which triggers the activation of a pathophysiological cascade. Pathophysiological processes accompanying the opening of the blood vessel include activation of catecholamines, RAS and neutrophils and subsequent free radical production, and increases in the levels of proinflammatory citokines and intracellular CA levels, that is, the so called oxygen paradox. The above mentioned processes can be blocked by beta receptor blockers (BRB) as demonstrated by class I, type A evidence. A number of clinical studies have shown their clinical efficiency following PCI. The PAMI, StentPAMI, AirPAMI and CADILLAC studies have proved that BRBs decrease mortality and morbidity after the intervention. The third-generation BRB carvedilol, which acts as a beta and alpha blocker in patients with STEMI successfully treated with PCI, and is also a Ca-channel blocker and a free radical trap, is the firstchoice agent for both theoretical and clinical reasons. Animal studies have shown that carvedilol results in greater reductions in the levels of markers indicating postinfarction reperfusion and ventricular remodeling (MCP1, MMP2, TIMP2) compared with metoprolol. Animal studies have also showed that carvedilol is the most efficient BRB for preventing the damaging of gap junction structure in reperfusion, and for inhibiting the ventricular arrhythmias induced by reperfusion, through restoring connexin 43. The beneficial effect of this drug on the cardiovascular events and mortality following myocardial infarction have been demonstrated in a number of human studies with hard endpoints. The unique efficiency of carvedilol in vascular prevention following PCI has been demonstrated by the short-term and longterm efficiency of carvedilol-filled stents, compared with BMSE-filled stents. Information on the postintervention, long-term (3-year) efficiency of carvedilol in a large (N :7500) patient group is expected to be published in 2015 in the CAPITAL-RCT study coordinated by the University of Kyoto. In summary, the results of experimental and clinical studies on carvedilol have shown that within the BRB group, carvedilol is highly recommended for the prevention of oxygen paradox following successful PCI and preserving the myocardium.]

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