Novel antidiabetic therapies in patients with peripheral artery disease: current perspective DOI Creative Commons
Miodrag Janić,

Viviana Maggio,

Andrej Janež

et al.

Frontiers in Clinical Diabetes and Healthcare, Journal Year: 2024, Volume and Issue: 5

Published: Nov. 26, 2024

1 IntroductionPeripheral artery disease (PAD) is the third leading cause of atherosclerosis-related morbidity, after coronary and cerebrovascular diseases. Approximations its prevalence are 10–26% in general adult population increase with age. PAD bears burden functional decline major adverse limb events (MALE), consisting chronic limb-threatening ischemia, acute amputations. Chronic ischemia associated 20% mortality amputations one year. The lifetime risk varies based on traditional factors, including diabetes, smoking, dyslipidaemia, hypertension, a sedentary lifestyle. inflammation, metals, air pollution, depression also seem to play role. Furthermore, albuminuria related leg retinopathy PAD, regardless duration diabetes haemoglobin A1c (HbA1c) levels (1). has an increased propensity not only for MALE, but significant cardiovascular (MACE). Coronary prevalent 30–50% patients while presence polyvascular further increases susceptibility MACE (2).Diabetes significantly affecting 20–28% people diabetes. crucial factor diabetic foot ulcers, 50% those ulcers have PAD. diagnosis ischaemia challenging due atypical symptoms, particularly absence intermittent claudication rest pain attributed peripheral neuropathy, medial calcification that affects precision non-invasive diagnostic tests. In progression differs from individuals without manifesting itself more distal arteries, multiple bilateral arterial segments, reducing collateral growth, thus increasing amputation. leads worse outcomes, non-healing gangrene, amputation, disease. Approximately 70% non-traumatic lower extremity United States can be this disproportional overall 12% (2, 3). Post-amputation severe, dying 5 years, comparable many cancers (4).As MALE MACE, comprehensive multidisciplinary management highest importance, comprising non-pharmacologic intervention (lifestyle modification: smoking cessation, supervised exercise therapy, Mediterranean diet, weight loss), pharmacologic (antihypertensive lipid lowering antithrombotic glucose therapy) invasive therapy (endovascular surgical revascularization) 5). Revascularization procedures performed improve local conditions; however, who undergone these still face higher compared their counterparts such (2). 2 New antidiabetic therapies diseaseNew consist mainly sodium-glucose cotransporter-2 inhibitors (SGLT2i) glucagon-like peptide 1-receptor agonists (GLP1-RA). Representatives drug classes been reduction type (6). However, main outcome trials, most enrolled had concomitant disease, were underrepresented Even though, proven risk, which goes beyond mere glycaemic control, drugs both benefit recommended by 2023 ESC Guidelines treatment 2024 aortic diseases as choice reduce independent baseline or target HbA1c (5, 7). SGLT2i effectively kidney heart failure patients, common comorbidities seen yet meta-analysis 20 trials did find impact incidence contrast, US databases linked 1.65-fold GLP-1RA. A similar signal was observed 1.97-fold canagliflozin. It should emphasized amputation canagliflozin CANVAS trial, confirmed CREDENCE trial. post hoc analysis trial revealed majority minor infection, dose Instead, primarily previous established factors despite specific identified etiological mechanism. anticipated number less than averted (8). Additionally, conducted Lin et al. showed treated exhibited modest use SGLT2i. This greater loss cohort, addition diastolic pressure pronounced reductions systolic blood pressures, all potential markers volume depletion (9). Thus, underlying mechanism contributes elevated diuretic-induced hypovolemia, provoked SGLT2i, resulting reduced perfusion extremities. hypoperfusion initiate tissue necrosis, subsequently diuretic effect question likely during initial phase (10). mentioned probably specifical (canagliflozin) class effect, there no other obvious (11). International Working Group Diabetic Foot advises against starting any drug-naïve gangrene suggests stopping until healing occurs, carefully balancing individual risk-benefit ratio (3). GLP-1RA within two years following commencement, decreased (12). finding aligns various putative anti-atherosclerotic mechanisms, enhancement systemic microcirculation, inflammation oxidative stress, well improvements endothelial function vasodilation (13). Some expected shed additionally (14). recent LEADER SUSTAIN-6 liraglutide semaglutide demonstrated consistent efficacy Consequently, it appears show evident superiority medications respect PAD-related (15). could emerge even obesity since SELECT 2,4 mg. included 8.6% (16). terms current emerging therapies, great anticipation SOUL event-driven, double-blind, placebo-controlled evaluated first oral GLP1-RA, (14 mg once daily) placebo, atherosclerotic and/or Among individuals, 15.7% symptomatic category mutually exclusive territories (17). Recent announcement 14% (18). tirzepatide, dual GIP/GLP-1 receptor agonist, being SURPASS-CVOT designed randomized, active-controlled outcomes People (25.3% PAD) subjected weekly subcutaneous injection tirzepatide up 15 1.5 dulaglutide. noninferiority time dulaglutide will confirm safety tirzepatied placebo determine whether produces active comparator (demonstrating superiority) (19). And analysing mostly indirect data, STARDUST daily 1.8 6 months directly detected transcutaneous oxygen (TcPO2) confirming prevention clinical (20). results STRIDE eagerly 52-week week would maximum walking distance constant load treadmill median pain-free 114 m (maximum 186 m). Secondary include quality life cardiometabolic parameters (21). ongoing objective evaluating (NCT04146155) 24 weeks distance.3 DiscussionThe field sufficiently explored demonstrate possible favourable benefits new therapies. Although shown definitive data come, effects validated. On contrary, wide range conditions populations exists lack direct evaluate effectiveness With certain negative indicators, may never occur, casting pessimistic outlook demographic patients. advent personalized medicine underscores importance tailoring approaches each patient. Therefore, imperative meticulously assess balance risks ensure beneficial does exclude patient much gain use.

Language: Английский

Association between serum retinol-binding protein and lower limb atherosclerosis risk in type 2 diabetes mellitus DOI

Yu-Ling Zhang,

Guiliang Peng, Weiling Leng

et al.

World Journal of Diabetes, Journal Year: 2025, Volume and Issue: 16(3)

Published: Jan. 20, 2025

BACKGROUND Serum retinol-binding protein (RBP) is the primary transport of circulating vitamin A. RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis. Several studies have indicated that serum participates progression diabetes diabetes-related complications. However, impact on lower limb atherosclerosis not been determined individuals with type 2 mellitus (T2DM). AIM To determine association between T2DM. METHODS This retrospective study enrolled 4428 eligible T2DM patients divided into non-lower (n = 1913) groups 2515) based arterial ultrasonography results. At hospital admission, baseline levels were assessed, all subjects categorized three (Q1-Q3) tertiles. Logistic regression, restricted cubic spline subgroup analysis, machine learning used to assess risk. RESULTS Among T2DM, 2515 (56.80%) had atherosclerosis. analysis showed risk increased by 1% for every 1 unit rise level (odds ratio 1.01, 95% confidence interval: 1.00-1.02, P 0.004). Patients highest tertile group (Q3) higher compared lowest (Q1) 1.36, 1.12-1.67, 0.002). The gradually an increase (P trend 0.005). Restricted linear correlation (non-linear < 0.05). Machine demonstrated significance diagnostic value predicting CONCLUSION Elevated correlate

Language: Английский

Citations

0
Ankle-Brachial Pressure Index Correlates with Abdominal Volume Index in Normal-Weight Type 2 Diabetes Mellitus Patients DOI

Sahar Mudassar,

Mumtaz Ali Lakho,

Rehan Anwar

et al.

Pakistan Journal of Health Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 337 - 342

Published: Jan. 31, 2025

Obesity significantly impacts glycemic control and vascular health in Type 2 diabetes mellitus. Objectives: To compare clinical characteristics, obesity indices, status between normal-weight obese/overweight mellitus patients. Methods: A cross-sectional study was conducted for six months from April 2024 to September at the Medicine Outpatient Department. This included 82 patients divided into two groups: (n=34) (n=48). Clinical parameters such as HbA1c, BMI, abdominal volume index, ankle-brachial pressure index (ABPI) were measured. Data analyzed by SPSS version 23.0. Results: Obese/overweight older (57.74 ± 8.57 vs. 52.81 9.41 years, p=0.018) had worse (HbA1c: 7.17 0.97% 6.51 0.68%, p = 0.0008) than Both BMI (30.57 3.39 23.13 1.80 kg/m²) AVI (16.44 1.58 11.84 1.61) higher group (both p<0.0001). Ankle-Brachial Pressure Index lower (0.93 0.15 0.99 0.08, p=0.033), suggesting poorer health. Negative correlations indices indicated adiposity linked dysfunction. Conclusions: It concluded that showed Abdominal age, duration independently predicted emphasizing need address mitigate risks T2

Language: Английский

Citations

0
The impact of individuals’ preventive behaviours on health and healthcare utilisation DOI Creative Commons

Aarushi Dhingra,

Gianluca Fiorentini, Luke B. Connelly

et al.

Economics & Human Biology, Journal Year: 2025, Volume and Issue: 57, P. 101486 - 101486

Published: April 5, 2025

We investigate the impact of preventative health behaviour an individual, colon screening, on outcomes and healthcare utilisation. employ instrumental variable approach to address circularity in this relationship, using eye examination as our instrument. Our instrument exploits fact that individuals who comply with recommendations or exhibit positive behaviours tend cluster for other well. use two-stage least square regressions data from Survey Health, Ageing Retirement Europe. The results show undertaking screening increases probability hospitalisations, especially those are planned. It also leads increase a diagnosis cancer cancer, while reducing death subsequent period. Heterogeneity checks provide evidence these driven mostly by females, unmarried individuals, people more than two co-morbidities lower education income. highlight need promote targeted information preventive medicine enhance early detection which may survival, reduce avoidable burden system, especially, amongst vulnerable groups.

Language: Английский

Citations

0
Cardiovascular Effectiveness and Safety of Antidiabetic Drugs in Patients with Type 2 Diabetes and Peripheral Artery Disease: Systematic Review DOI Creative Commons
Antonio Cimellaro,

Michela Cavallo,

Marialaura Mungo

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(9), P. 1542 - 1542

Published: Sept. 20, 2024

Peripheral artery disease (PAD) is an atherosclerotic condition commonly complicating type 2 diabetes (T2D), leading to poor quality of life and increased risk major adverse lower-limb (MALE) cardiovascular (CV) events (MACE). Therapeutic management PAD in T2D patients much more arduous, often due bilateral, multi-vessel, distal vascular involvement, addition systemic polyvascular burden. On the other hand, pathophysiological link between very complex, involving mechanisms such as endothelial dysfunction subclinical inflammation chronic hyperglycemia. Therefore, clinical approach should not ignore protection with aim reducing limb overall CV besides a mere glucose-lowering effect. However, choice best medications this setting challenging low-grade evidence or lacking targeted studies patients. The present review highlighted strong relationship PAD, focusing on treatment strategy reduce prevent occurrence worsening T2D. Medline databases were searched for including up June 2024 reporting effectiveness safety most used agents, no restriction definition, study design, country. main outcomes considered MACE—including nonfatal acute myocardial infarction, stroke, death—and MALE—defined complications, amputations, need revascularization. To our current knowledge, GLP-1 receptor agonists SGLT2 inhibitors represent settings, but personalized be considered. preferred subjects prevalent burden history previous MALE, while those heart failure if benefits outweigh complications.

Language: Английский

Citations

1
Novel antidiabetic therapies in patients with peripheral artery disease: current perspective DOI Creative Commons
Miodrag Janić,

Viviana Maggio,

Andrej Janež

et al.

Frontiers in Clinical Diabetes and Healthcare, Journal Year: 2024, Volume and Issue: 5

Published: Nov. 26, 2024

1 IntroductionPeripheral artery disease (PAD) is the third leading cause of atherosclerosis-related morbidity, after coronary and cerebrovascular diseases. Approximations its prevalence are 10–26% in general adult population increase with age. PAD bears burden functional decline major adverse limb events (MALE), consisting chronic limb-threatening ischemia, acute amputations. Chronic ischemia associated 20% mortality amputations one year. The lifetime risk varies based on traditional factors, including diabetes, smoking, dyslipidaemia, hypertension, a sedentary lifestyle. inflammation, metals, air pollution, depression also seem to play role. Furthermore, albuminuria related leg retinopathy PAD, regardless duration diabetes haemoglobin A1c (HbA1c) levels (1). has an increased propensity not only for MALE, but significant cardiovascular (MACE). Coronary prevalent 30–50% patients while presence polyvascular further increases susceptibility MACE (2).Diabetes significantly affecting 20–28% people diabetes. crucial factor diabetic foot ulcers, 50% those ulcers have PAD. diagnosis ischaemia challenging due atypical symptoms, particularly absence intermittent claudication rest pain attributed peripheral neuropathy, medial calcification that affects precision non-invasive diagnostic tests. In progression differs from individuals without manifesting itself more distal arteries, multiple bilateral arterial segments, reducing collateral growth, thus increasing amputation. leads worse outcomes, non-healing gangrene, amputation, disease. Approximately 70% non-traumatic lower extremity United States can be this disproportional overall 12% (2, 3). Post-amputation severe, dying 5 years, comparable many cancers (4).As MALE MACE, comprehensive multidisciplinary management highest importance, comprising non-pharmacologic intervention (lifestyle modification: smoking cessation, supervised exercise therapy, Mediterranean diet, weight loss), pharmacologic (antihypertensive lipid lowering antithrombotic glucose therapy) invasive therapy (endovascular surgical revascularization) 5). Revascularization procedures performed improve local conditions; however, who undergone these still face higher compared their counterparts such (2). 2 New antidiabetic therapies diseaseNew consist mainly sodium-glucose cotransporter-2 inhibitors (SGLT2i) glucagon-like peptide 1-receptor agonists (GLP1-RA). Representatives drug classes been reduction type (6). However, main outcome trials, most enrolled had concomitant disease, were underrepresented Even though, proven risk, which goes beyond mere glycaemic control, drugs both benefit recommended by 2023 ESC Guidelines treatment 2024 aortic diseases as choice reduce independent baseline or target HbA1c (5, 7). SGLT2i effectively kidney heart failure patients, common comorbidities seen yet meta-analysis 20 trials did find impact incidence contrast, US databases linked 1.65-fold GLP-1RA. A similar signal was observed 1.97-fold canagliflozin. It should emphasized amputation canagliflozin CANVAS trial, confirmed CREDENCE trial. post hoc analysis trial revealed majority minor infection, dose Instead, primarily previous established factors despite specific identified etiological mechanism. anticipated number less than averted (8). Additionally, conducted Lin et al. showed treated exhibited modest use SGLT2i. This greater loss cohort, addition diastolic pressure pronounced reductions systolic blood pressures, all potential markers volume depletion (9). Thus, underlying mechanism contributes elevated diuretic-induced hypovolemia, provoked SGLT2i, resulting reduced perfusion extremities. hypoperfusion initiate tissue necrosis, subsequently diuretic effect question likely during initial phase (10). mentioned probably specifical (canagliflozin) class effect, there no other obvious (11). International Working Group Diabetic Foot advises against starting any drug-naïve gangrene suggests stopping until healing occurs, carefully balancing individual risk-benefit ratio (3). GLP-1RA within two years following commencement, decreased (12). finding aligns various putative anti-atherosclerotic mechanisms, enhancement systemic microcirculation, inflammation oxidative stress, well improvements endothelial function vasodilation (13). Some expected shed additionally (14). recent LEADER SUSTAIN-6 liraglutide semaglutide demonstrated consistent efficacy Consequently, it appears show evident superiority medications respect PAD-related (15). could emerge even obesity since SELECT 2,4 mg. included 8.6% (16). terms current emerging therapies, great anticipation SOUL event-driven, double-blind, placebo-controlled evaluated first oral GLP1-RA, (14 mg once daily) placebo, atherosclerotic and/or Among individuals, 15.7% symptomatic category mutually exclusive territories (17). Recent announcement 14% (18). tirzepatide, dual GIP/GLP-1 receptor agonist, being SURPASS-CVOT designed randomized, active-controlled outcomes People (25.3% PAD) subjected weekly subcutaneous injection tirzepatide up 15 1.5 dulaglutide. noninferiority time dulaglutide will confirm safety tirzepatied placebo determine whether produces active comparator (demonstrating superiority) (19). And analysing mostly indirect data, STARDUST daily 1.8 6 months directly detected transcutaneous oxygen (TcPO2) confirming prevention clinical (20). results STRIDE eagerly 52-week week would maximum walking distance constant load treadmill median pain-free 114 m (maximum 186 m). Secondary include quality life cardiometabolic parameters (21). ongoing objective evaluating (NCT04146155) 24 weeks distance.3 DiscussionThe field sufficiently explored demonstrate possible favourable benefits new therapies. Although shown definitive data come, effects validated. On contrary, wide range conditions populations exists lack direct evaluate effectiveness With certain negative indicators, may never occur, casting pessimistic outlook demographic patients. advent personalized medicine underscores importance tailoring approaches each patient. Therefore, imperative meticulously assess balance risks ensure beneficial does exclude patient much gain use.

Language: Английский

Citations

1