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.]



Further articles in this publication

Lege Artis Medicinae

[Experience with coenzyme Q10 in heart failure]

KOHUT László

[INTRODUCTION - The protein complex coenzyme Q10 (CoQ10) has a role in ATP production as a mitochondrial electron transport molecule, and it also has a strong antioxidant effect. Several studies have proved the correlation between the decrease in CoQ10 level and the severity of heart failure. Heart failure is a multifactorial syndrome, the development of which is greatly influenced by an abnormal energy metabolism. CASE REPORT - The 61-year-old woman developed heart failure after a myocardial infarction. She complained of fatigue, dyspnoea and reduced physical endurance even with optimal treatment. When her therapy was completed by CoQ10, her endurance and life quality significantly improved and her symptoms ameliorated. CONCLUSIONS - Medical treatment of chronic heart failure is an evidence-based, complex therapy. Despite the complex management, morbidity and mortality of this condition remain high. A number of studies have shown that CoQ10 substitution can improve the clinical and haemodynamical parameters of patients with heart failure. On the basis of these results, the use of CoQ10 as an adjuvant therapy to complex treatment has an increasing role.]

Lege Artis Medicinae

[Junk food tax: he that says a, should also say D!]


Lege Artis Medicinae

[Fulvestrant therapy of advanced breast cancer]


Lege Artis Medicinae

[The use of carvedilol following invasive interventions]


[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.]

Lege Artis Medicinae

[Apoplexia in medulla oblongata]


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[Purpose - To evaluate the efficacy and safety of gabapentin (GBP) in idiopathic or crypto/symptomatic partial epilepsy in adults. Methods - We performed a prospective open label add-on study in pharmacoresistant patients with simple or complex partial or generalized seizures of partial onset (at least four seizures per month). GBP was added to no more than two baseline antiepileptics and the efficacy was rated primarily according to the seizure frequency. The secondary efficacy parameters were the change in the seizure severity scores (measured by the NHS3 scale) and in the quailty of life (measured by the QUOLIE-31 questionnaire). GBP was added up to 1500-1600 mg per day in the titration period than an individual optimalization was allowed in any further visits. The follow-up period was three months. Population - Fourteen Hungarian epilepsy out-patient unit participated in the study. 72 patients were enrolled, GBP was applied in 63 persons (ITT population) and 57 completed the study. Results - A more than 50% decrease in seizure frequency was found in more than 70% of the patients in the third month. Among them just every third patient became seizure-free. Significant improvement appeared also in the severity of seizures and in the total score of the quality of life questionnaire. There was no difference either according to the etiology of the epilepsy or the seizure types. GBP was tolerated excellently. There was no need to decrease of the dosage of GBP and the side effects were mild and of transitory nature. Consequences - GBP appears to be a valuable antiepileptic drug considering its high efficacy and extremely favourable tolerance. While GBP also decreases the severity of the seizures, its complex effects result an improvement in the quality of life of the patients. The positive effects have been durable during the follow-up. Open label naturalistic studies of larger population are needed to clear the special indications of GBP in chronic partial epilepsies.]

Lege Artis Medicinae

[The place of sulphonylurea compounds in the blood glucose lowering therapy of type 2 diabetes]


[The mechanism of blood glucose lowering action of sulphonylureas, their advantages and potencial risks are overviewd in the article. The author delineates the present place of the sulphonylurea group in the antihyperglycemic therapy of type 2 diabetes, listing possibilities of monotherapeutic as well as combined applications. It is emphasized that traditional insulin-secretagogue compounds have their place in the therapy of type 2 diabetes even beside of the new, incretin-type secretagogues.]

Lege Artis Medicinae


UNGUREAN Aurélia, TAJTI János, VÉCSEI László

[Migraine sufferers in Hungary present a major epidemiological challenge with about 12% of the population affected. Authors have reviewed an extensive body of internationally published literature relative to the 5-hydroxi-triptamin receptor agonists such as the triptans. While summarising most relevant data with a view to enable physicians to choose the most effective therapy for an individual, the article also discusses the prevailing questions of efficacy, tolerability and safety. For those patients with differential-diagnostic difficulties referrals should be made to the specialized 'headache centers' of neurological departments.]

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[Nebivolol: the long-acting, vasodilatator beta-blocker]


[Nebivolol is a third-generation, long-acting, vasodilator beta-adrenoceptor-blocker with very high selectivity to beta-1 receptor. In addition to its efficient blood pressure lowering effect, results of previous trials have shown that nebivolol, which has a vasodilator effect and improves endothelial dysfunction, offers a safe, well-tolerable therapeutic option for elderly patients with heart failure, chronic pulmonary disease, diabetes, hyperlipidaemia and hypertension. It does not affect or improves lipid and carbohydrate metabolism, moreover, it can improve patients’ quality of life in multiple ways.]

Lege Artis Medicinae

[Biosimilar insulins on the horizon]


[Nowadays human insulins and insulin analogues are exclusively used in the clinical practice, when insulin therapy is needed. The patents of human insulins are expired and will expire soon for glargine, the first long-acting, basal insulin analogue preparation. The reliable production of biosimilar insulins is a new challenge for the pharmaceutical industry. Independently developed insulins with appreciable clinical efficacy have already become available in some countries where the quality criteria of regulatory process in place are less strict than in the European Union. The first approval for true biosimilar insulin, i.e. for biosimilar glargine was given in Europe in 2014. In this article, the characteristics of biosimilar insulins, especially the difficulties in the manufacturing process are reviewed in comparison with generic drugs. It is of note that potential efficacy and safety differences may occur due to even minor changes in the production, formulation and storage of the biological drugs. Therefore, biosimilarity should be investigated by detailed comparative pharmacokinetic and pharmacodynamic studies. Moreover, similar clinical efficacy and safety should be documented by randomized, comparative clinical trials. The potential impact of altered immunologic profile of biosimilar insulins should also be carefully monitored. ]