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Glavni cilj zdravljenja sladkorne bolezni tipa 2 (SB2) je preprečevanje kroničnih zapletov sladkorne bolezni, tj. mikrovaskularnih in srčno-žilnih (makrovaskularnih) zapletov. Farmakoterapija SB2 se je v zadnjem desetletju precej spremenila, predvsem na račun razvoja novejših antihiperglikemičnih zdravil iz skupin zaviralcev dipeptidil peptidaze 4 (DPP-4), analogov glukagonu podobnega peptida 1 (GLP-1) in zaviralcev natrijevih glukoznih koprenašalcev 2 (SGLT2). Klinične študije, na podlagi katerih so ta zdravila pridobila dovoljenje za promet, so vrednotile kratkoročne klinične izide zdravljenja (delež glikiranega hemoglobina), ne pa tudi dolgoročnih (npr. pojavnosti srčno-žilnih zapletov, mikrovaskularnih zapletov). Od leta 2008 Agencija za hrano in zdravila v ZDA (ang. Food and Drug Administration – FDA) za vsa novejša antihiperglikemična zdravila po prihodu na trg zahteva predložitev podatkov o srčno-žilni varnosti, saj se je za učinkovino iz skupine tiazolidindionov, rosiglitazon, izkazalo, da poveča tveganje za miokardni infarkt. Za dokazovanje srčno-žilne varnosti je bilo izvedenih veliko kliničnih študij, t. i. študij srčno-žilne varnosti (ang. cardiovascular outcomes trials – CVOT), katerih namen je bil dokazati, da posamezno antihiperglikemično zdravilo ne poveča tveganja za srčno-žilne dogodke v primerjavi s placebom. Čeprav so študije CVOT primarno zasnovane za vrednotenje varnostnega vidika zdravljenja z novejšimi antihiperglikemičnimi zdravili, so nekatere pokazale celo ugoden vpliv določenih učinkovin iz skupin zaviralcev SGLT2 in analogov GLP-1 na zmanjšanje pojavnosti pomembnih neželenih srčno-žilnih dogodkov (ang. major adverse cardiovascular events – MACE). Učinkovine iz skupine zaviralcev SGLT2 so zmanjšale tudi tveganje za hospitalizacijo zaradi srčnega popuščanja. Ker so te študije vključevale bolnike s SB2 in obstoječo srčno-žilno boleznijo oziroma prisotnimi dejavniki tveganja za srčno-žilni dogodek, so rezultati prenosljivi le na manjši delež bolnikov s SB2 v klinični praksi. Vpliv antihiperglikemičnih zdravil na pojavnost tako srčno-žilnih kot tudi mikrovaskularnih zapletov pri bolnikih s SB2 v klinični praksi bi lahko najhitreje in najučinkoviteje ovrednotili z opazovalnimi raziskavami. The main goal of treatment of type 2 diabetes (T2D) is to prevent its long-term chronic complications, especially microvascular and cardiovascular (macrovascular) complications. Pharmacotherapy of T2D has changed significantly over the past decade, mainly due to the market introduction of novel classes of antidiabetic medicines: dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i). The clinical trials based on which these antidiabetic medicines obtained marketing authorisation evaluated short-term (e.g. levels of glycated haemoglobin, HbA1c) rather than long-term clinical outcomes (e.g. incidence of cardiovascular and microvascular complications). Since 2008, however, the US Food and Drug Administration has mandated that cardiovascular safety data be submitted for all novel antidiabetic medicines entering the market, as one of the medicines in the thiazolidinedione group – rosiglitazone – has been shown to increase the risk of myocardial infarction. To this end, many post-marketing clinical trials, known as cardiovascular outcome trials (CVOTs), have been conducted to date with the aim of demonstrating that, compared to placebo, the individual antidiabetic medicine is not associated with an increased risk of cardiovascular events. Although these trials were primarily designed to evaluate the safety aspects of novel antidiabetic medicines, some have even shown a beneficial effect of medicines from the SGLT2i and GLP-1RA drug classes in reducing the risk of major adverse cardiovascular events (MACE). Medicines from the SGLT2i drug class also reduced the risk of hospitalisation due to heart failure. However, these studies included patients with established cardiovascular disease and patients with cardiovascular risk factors who had not yet developed cardiovascular disease. Therefore, the results of the studies can only be generalised to a small proportion of patients with T2D in routine clinical practice. The effect of antidiabetic medicines on the risk of both cardiovascular and microvascular complications in patients with T2D in routine clinical practice could be assessed most rapidly and effectively with observational studies.

Background: We examined the role of rs1333049 polymorphism of the CDKN2B Antisense RNA 1 (CDKN2B-AS1) on the prevalence of myocardial infarction (MI) in Slovenian subjects with type 2 diabetes mellitus (T2DM). Methods: A total of 1071 subjects with T2DM were enrolled in this retrospective cross-sectional case-control study. Of the subjects, 334 had a history of recent MI, and 737 subjects in the control group had no clinical signs of coronary artery disease (CAD). With logistic regression, we performed a genetic analysis of rs1333049 polymorphism in all subjects. Results: The C allele of rs1333049 polymorphism was statistically more frequent in MI subjects (p = 0.05). Subjects with CC genotype had a higher prevalence of MI than the control group in the co-dominant (AOR 1.50, CI 1.02–2.21, p = 0.04) and recessive (AOR 1.38, CI 1.09–1.89, p = 0.04) genetic model. Conclusions: According to our study, the C allele and CC genotype of rs1333049 polymorphism of CDKN2B-AS1 are possible markers of MI in T2DM subjects in the Slovenian population.

Uvod: Življenjski slog z zdravim načinom prehranjevanja, zadostno telesno dejavnostjo in primerno telesno težo, je osnovni ukrep v zdravljenju sladkorne bolezni tipa 2 (SB2). Čeprav redna telesna dejavnost lahko prepreči ali odloži pojav bolezni in njenih zapletov, večina bolnikov s SB2 ni telesno dejavnih. Kot glavni razlog največkrat navajajo pomanjkanje časa. Visoko intezivna intervalna vadba (VIIV) je vadba z izmenjavo ponavljajočih se visoko in nizko intenzivnih intervalov telesne dejavnosti. Številne raziskave dokazujejo, da je VIIV zelo učinkovita za izboljšanje kardiorespiratorne pripravljenosti, endotelne funkcije, inzulinske senzitivnosti ter doseganje metaboličnih prilagoditev skeletne mišice. Namen: Namen diplomskega dela je bil, na podlagi pregleda literature, ugotoviti učinke visoko intenzivne intervalne vadbe na bolnike s SB2, ter primerjati visoko intenzivno intervalno vadbo s kontinuirano aerobno vadbo pri bolnikih s SB2. Metode dela: Pregledane so bile podatkovne zbirke: Medline (preko baze EBSCOhost), The Cochrane Library, PeDRO in Scopus, na Zdravstveni fakulteti, Medicinski fakulteti in preko oddaljenega dostopa. Rezultati: V podroben pregled smo na podlagi zastavljenih kriterijev vključili 7 raziskav. V primeru glikemičnega nadzora, sistoličnega krvnega tlaka, vrednosti holesterola in ITM se je VIIV izkazala za bolj učinkovito v primerjavi s kontinuirano aerobno vadbo, pri bolnikih s SB2, ko je vadba potekala 12-16 tednov. Razprava in sklep: V našem pregledu smo ugotovili, da sta obe obliki vadbe, zmerna kontinuirana aerobna in VIIV, koristni za bolnike s SB2, le da z VIIV dosežemo primerljive učinke v krajšem času. Vendar je VIIV bolj učinkovita v primeru glikemične kontrole, sistoličnega krvnega tlaka, vrednosti holesterola in ITM. Še več, v nobeni raziskavi niso preiskovanci iz skupine VIIV utrpeli poškodb ali miokardni infarkt, kar kaže na varno uporabo VIIV pri tej skupini bolnikov. Glede na dejstvo, da je pomanjkanje časa največkrat navedena ovira za redno telesno dejavnost, se zdi da je VIIV varna in učinkovita alternativa tradicionalni kontinuirani aerobni vadbi. Introduction: Lifestyle modification regarding a healthy diet, adequate physical activity and optimal weight control remains the cornestone in the prevention, management and treatment of the type 2 diabetes. Although regular physical activity can prevent or delay the onset of the disease and its complications, most patients with type 2 diabetes are not physically active. Lack of time is the number-one reported barrier to regular exercise participation. High intensity interval training is comprised of brief periods of high-intensity exercise interposed with recovery periods at a lower intensity. There is accumulating evidence that a variety of high intensity interval training protocols are highly effective at improving cardiorespiratory fitness, endothelial function, muscle metabolic capacity and insulin sensitivity. Purpose: The main purpose of this thesis is to review randomized control trials in order to establish the effectiveness of high intensity interval training in patients with type 2 diabetes and to compare feasibility of high intensity interval and moderate intensity continuous exercise training in patients with type 2 diabetes. Methods: RCT were identified through databases Medline (EBSCOhost), The Cochrane Library, PeDRO and Scopus. Results: The review included 7 studies. High intensity interval training appears to promote superior improvements in the case of glycemic control, systolic blood pressure, cholesterol and BMI values in comparison to moderate intensity continuous exercise, when performed by patients with type 2 diabetes for at least 12-16 weeks. Conclusion: In our review, we found that both exercise modes, moderate intensity continuous exercise and high intensity interval training were useful for patients with type 2 diabetes, with the high intensity interval training achieving comparable effects in a shorter time. However, high intensity interval training is more effective in the case of glycemic control, lowering systolic blood pressure, cholesterol and ITM values. High intensity interval training involves a substantially lower total exercise volume and time commitment and has therefore been touted as a time-efficient exercise option. Given that lack of time is the number-one reported barrier to regular exercise participation, it is possible that high intensity interval training may be an attractive and safe option for increasing physical activity levels in patients with type 2 diabetes.