Diabetes mellitus is a major healthcare problem. It is not only characterized by hyperglycemia and chronic complications, but in longer lasting diabetes and a longer living population, it is also ...associated with accelerated arterial ageing, which importantly contributes to cardiovascular complications. The accelerated arterial ageing in patients with diabetes should be considered separately from arterial ageing in patients without diabetes. Basic and clinical research have allowed better insight into the mechanisms of arterial ageing. In a simplified mechanistic way, it could be considered that the three tightly connected cornerstone characteristics of arterial ageing in patients with diabetes are: phenotypic presentation as endothelial dysfunction and arterial stiffness, and the underlying basic ageing-facilitating mechanism represented as the impaired expression of genetic longevity pathways. Currently, specific drugs for preventing/treating arterial ageing are not available. Therefore, we aimed to review the capacity of available drugs, particularly antidiabetic drugs, to interfere with the arterial ageing process. In the near future, these characteristics could help to guide therapy in patients with diabetes. Overall, it appears that arterial ageing could become a new target in diabetes. The expanding knowledge regarding the capability of antidiabetic drugs and other available drugs to inhibit/delay arterial aging is therefore essential.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The world population is aging and the number of old people is continuously increasing. Arterial structure and function change with age, progressively leading to arterial stiffening. Arterial ...stiffness is best characterized by measurement of pulse wave velocity (PWV), which is its surrogate marker. It has been shown that PWV could improve cardiovascular event prediction in models that included standard risk factors. Consequently, it might therefore enable better identification of populations at high-risk of cardiovascular morbidity and mortality. The present review is focused on a survey of different pharmacological therapeutic options for decreasing arterial stiffness. The influence of several groups of drugs is described: antihypertensive drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, diuretics, and nitrates), statins, peroral antidiabetics, advanced glycation end-products (AGE) cross-link breakers, anti-inflammatory drugs, endothelin-A receptor antagonists, and vasopeptidase inhibitors. All of these have shown some effect in decreasing arterial stiffness. Nevertheless, further studies are needed which should address the influence of arterial stiffness diminishment on major adverse cardiovascular and cerebrovascular events (MACCE).
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Deteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We ...explored the possible effects of empagliflozin's effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients.
Forty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively). The fourth group received placebo. Arterial function was assessed at inclusion and after 12 weeks treatment by: endothelial function brachial artery flow-mediated dilation (FMD), reactive hyperaemia index (RHI), arterial stiffness pulse wave velocity (PWV) and common carotid artery stiffness (β-stiffness). For statistical analysis one-way analysis of variance with Bonferroni post-test was used.
Empagliflozin on top of metformin treatment significantly improved endothelial function as did metformin after 12 weeks of treatment: FMD 2.6-fold (P < 0.001) vs. 1.8-fold (P < 0.05) and RHI 1.4-fold (P < 0.01) vs. 1.3-fold (P < 0.05). Empagliflozin on top of metformin treatment was superior to metformin in improving arterial stiffness parameters; it significantly improved PWV and β-stiffness compared to metformin by 15.8% (P < 0.01) and by 36.6% (P < 0.05), respectively. Metformin alone did not influence arterial stiffness.
Empagliflozin on top of metformin treatment significantly improved arterial stiffness compared to metformin in T1DM patients. Endothelial function was similarly improved in all treatment groups. Empagliflozin seems to possess a specific capacity to decrease arterial stiffness, which could support its cardioprotective effects observed in large clinical studies. Trial registration Clinical trial registration: NCT03639545.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To explore the effects of oral semaglutide on glycaemic parameters, body weight, and satisfaction in the first recipient patients with type 2 diabetes mellitus in Slovenia, in a real-world ...clinical practice setting.
Methods
The first consecutive adult patients with type 2 diabetes who were eligible for oral semaglutide treatment were included in this prospective, open-label interventional study. Patients received increasing doses of oral semaglutide and were evaluated at inclusion, at 1 month, then 3–5 months after starting treatment. Fasting blood glucose, glycosylated haemoglobin (HbA1c), body weight, patient satisfaction with oral semaglutide treatment (using the validated Treatment Satisfaction Questionnaire for Medication), and adverse effects, were analysed. Statistical analyses were performed using one-way analysis of variance, and, when significant interactions were found, Bonferroni post-hoc test. A P-value <0.05 was considered statistically significant.
Results
Twenty patients (11 male: 9 female; mean age, 59.9 ± 1.5 years; mean diabetes duration, 8.5 ± 1.4 years) were included. Oral semaglutide (7 and 14 mg) significantly decreased HbA1c (from 9.4 ± 0.3% to 8.2 ± 0.2% and 7.8 ± 0.2%, respectively) and fasting plasma glucose (from 11.2 ± 0.5 mmol/L to 9.2 ± 0.7 mmol/L and 8.9 ± 0.4 mmol/L, respectively). Oral semaglutide (14 mg) significantly decreased body weight (from 100.9 ± 2.7 kg to 92.7 ± 2.4 kg). Patients reported that treatment was easy to use and expressed high global satisfaction. Mild and transient, mostly gastrointestinal, adverse effects were reported in 10 patients.
Conclusions
Oral semaglutide, the first oral glucagon-like peptide 1 receptor agonist, was effective and safe, and associated with high patient satisfaction, in its first recipients in Slovenia. The results are important for daily clinical practice involving patients with type 2 diabetes, however, due to the small study population, lack of placebo control, and short exposure to oral semaglutide, the effectiveness of oral semaglutide in clinical practice requires further investigation.
In diabetic patients, cardiomyopathy is an important cause of heart failure, but its pathophysiology has not been completely understood thus far. Myocardial hypertrophy and diastolic dysfunction have ...been considered the hallmarks of diabetic cardiomyopathy (DCM), while systolic function is affected in the latter stages of the disease. In this article we propose the potential pathophysiological mechanisms responsible for myocardial hypertrophy and increased myocardial stiffness leading to diastolic dysfunction in this specific entity. According to our model, increased myocardial stiffness results from both cellular and extracellular matrix stiffness as well as cell⁻matrix interactions. Increased intrinsic cardiomyocyte stiffness is probably the most important contributor to myocardial stiffness. It results from the impairment in cardiomyocyte cytoskeleton. Several other mechanisms, specifically affected by diabetes, seem to also be significantly involved in myocardial stiffening, i.e., impairment in the myocardial nitric oxide (NO) pathway, coronary microvascular dysfunction, increased inflammation and oxidative stress, and myocardial sodium glucose cotransporter-2 (SGLT-2)-mediated effects. Better understanding of the complex pathophysiology of DCM suggests the possible value of drugs targeting the listed mechanisms. Antidiabetic drugs, NO-stimulating agents, anti-inflammatory agents, and SGLT-2 inhibitors are emerging as potential treatment options for DCM.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In Diabetes Mellitus (DM), hyperglycaemia and insulin resistance progressively lead to both microvascular and macrovascular complications. Whereas the incidence of microvascular complications is ...closely related to tight glycaemic control, this does not apply to macrovascular complications. Hyperglycaemia influences many interweaving molecular pathways that initially lead to increased oxidative stress, increased inflammation and endothelial dysfunction. The latter represents the initial in both types of vascular complications; it represents the "obligatory damage" in microvascular complications development and only "introductory damage" in macrovascular complications development. Other risk factors, such as arterial hypertension and dyslipidaemia, also play an important role in the progression of macrovascular complications. All these effects accumulate and lead to functional and structural arterial wall damage. In the end, all factors combined lead to the promotion of atherosclerosis and consequently major adverse cardiovascular events. If we accept the pivotal role of vascular wall impairment in the pathogenesis and progression of microvascular and macrovascular complications, treatment focused directly on the arterial wall should be one of the priorities in prevention of vascular complications in patients with DM. In this review, an innovative approach aimed at improving arterial wall dysfunction is described, which may show efficacy in clinical studies. In addition, the potential protective effects of current treatment approaches targeting the arterial wall are summarised.
Psoriasis is a chronic systemic inflammatory disease. Due to systemic inflammation, it is associated with many comorbidities. Among them, cardiovascular diseases represent the most common causes of ...morbidity and mortality in this population. Therefore, physicians treating patients with psoriasis should keep in mind that, as important as the treatment of psoriasis, awareness of cardiovascular risk deserves additional attention. Thus, in parallel with psoriasis treatment, a cardiovascular risk assessment must also be performed and addressed accordingly. In addition to encouraging non-pharmacologic strategies for a healthy lifestyle, physicians should be familiar with different pharmacologic options that can target psoriasis and reduce cardiovascular risk. In the present article, we present the pathophysiological mechanisms of the psoriasis and cardiometabolic interplay, our view on the interaction of psoriasis and cardiovascular disease, review the atherosclerotic effect of therapeutic options used in psoriasis, and vice versa, i.e., what the effect of medications used in the prevention of atherosclerosis could be on psoriasis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The incidence of aging-related disorders may be decreased through strategies influencing the expression of longevity genes. Although numerous approaches have been suggested, no effective, safe, and ...easily applicable approach is yet available. Efficacy of low-dose fluvastatin and valsartan, separately or in combination, on the expression of the longevity genes in middle-aged males, was assessed. Stored blood samples from 130 apparently healthy middle-aged males treated with fluvastatin (10 mg daily), valsartan (20 mg daily), fluvastatin-valsartan combination (10 and 20 mg, respectively), and placebo (control) were analyzed. They were taken before and after 30 days of treatment and, additionally, five months after treatment discontinuation. The expression of the following longevity genes was assessed:
,
,
,
,
, and
. Treatment with fluvastatin and valsartan in combination significantly increased the expression of
(1.8-fold;
< 0.0001),
(1.5-fold;
= 0.262) and
(1.7-fold;
< 0.0001), but not
,
and
. Both fluvastatin and valsartan alone significantly, but to a lesser extent, increased the expression of
, and did not influence the expression of other genes. Five months after treatment discontinuation, genes expression decreased to the basal levels. In addition, analysis with previously obtained results revealed significant correlation between
and both increased telomerase activity and improved arterial wall characteristics. We showed that low-dose fluvastatin and valsartan, separately and in combination, substantially increase expression of
,
, and
genes, which may be attributed to their so far unreported pleiotropic beneficial effects. This approach could be used for prevention of ageing (and longevity genes)-related disorders.
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Common inflammatory ground links obesity, insulin resistance, and asthma. As recognition of their interplay, one worsening the natural course of the other, is recognised, questions remain about how ...to adequately address them altogether to improve clinical outcomes. The present manuscript sheds light on the problem, describing possible pathophysiological links, clinical views, and therapeutic challenges, raising questions about what remains to be done, and calling for multidisciplinary treatment of these patients to detect diseases early and adequately address them before they become full-blown and deteriorate their health and quality of life.
Zaviralci natrij-glukoznega koprenašalnega sistema-2 (SGLT-2) se vse pogosteje predpisujejo tako v diabetologiji kot tudi v drugih internističnih strokah. Primarno ugodno vplivajo na presnovne ...dejavnike, tj. parametre glikemije in na telesno maso. Poleg tega omogočajo zaščito tarčnih organov, srčno-žilnega sistema in ledvic, pri osebah s sladkorno boleznijo ali brez nje. Neželeni učinki ob zdravljenju z zaviralci SGLT-2 so redki, večinoma nenevarni in jih lahko preprečimo. Zelo redek, a življenje ogrožajoč zaplet je lahko pojav diabetične ketoacidoze. Dejavnikov, ki povečajo tveganje za njen nastanek, še niso popolnoma raziskali. V prispevku so opisani diabetična ketoacidoza in njene posebnosti ob zdravljenju z zaviralci SGLT-2 ter možni vzročni dejavniki zanjo. Poznavanje slednjih je predvsem pomembno zaradi možnosti aktivnega preprečevanja diabetične ketoacidoze. Najpogosteje se pojavi hkrati z zdravljenjem z zaviralci SGLT-2 ob okužbah, sladkorni bolezni tipa 1, opustitvi inzulinskega zdravljenja ter v primerih stradanja. Prispevek vključuje tudi prikaz serije primerov, ki so bili hospitalizirani na našem kliničnem oddelku zaradi diabetične ketoacidoze ob zdravljenju z zaviralci SGLT-2, ob različni sočasni antidiabetični terapiji.
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