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Review
. 2024 Jun 26;23(1):220.
doi: 10.1186/s12933-024-02325-9.

Challenges and opportunities in the management of type 2 diabetes in patients with lower extremity peripheral artery disease: a tailored diagnosis and treatment review

Guillaume Mahé  1   2   3 , Victor Aboyans  4   5 , Emmanuel Cosson  6   7 , Kamel Mohammedi  8   9 , Gabrielle Sarlon-Bartoli  10   11 , Damien Lanéelle  12   13 , Tristan Mirault  14   15 , Patrice Darmon  11   16
Affiliations
Review

Challenges and opportunities in the management of type 2 diabetes in patients with lower extremity peripheral artery disease: a tailored diagnosis and treatment review

Guillaume Mahé et al. Cardiovasc Diabetol. .

Abstract

Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i.

Keywords: Glycemic control; Guidelines; Management; Peripheral artery disease; Type 2 diabetes.

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Conflict of interest statement

GM reports consulting fees from Novartis and Amgen; honoraria for lectures and presentations from Amarin, Aspen, Bayer, BMS-Pfizer, Leo Pharma, and Perimed; and advisory board participation for Novo Nordisk and Sanofi. VA reports honoraria and institutional funding from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Organon, Novo Nordisk, and Vifor. EC declares consulting fees, honoraria for lectures, presentations, or speaker bureaus from Abbott, AlphaDiab, Ascencia, Lilly, LVL Médical, Medtronic, MSD, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi-Aventis, as well as grants from AstraZeneca, LVL Médical, and Roche Diagnostics outside the submitted work. KM reports consulting fees from Novo Nordisk; honoraria for lectures, presentations, or speaker bureaus from Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Sanofi, LifeScan, Abbott, and Bayer; and advisory board participation for Novo Nordisk, Sanofi, and Amarin. GSB reports honoraria for lectures, presentations, or speaker bureaus from Amgen, BMS, Leo Pharma, Novartis, Novo Nordisk, Pfizer, Sanofi, and Servier. DL reports honoraria for lectures, presentations, or speaker bureaus from Amgen, Aspen, Bayer, BMS, Leo Pharma, Pfizer, and Sanofi. TM reports receiving honoraria from Bayer, Incyte, Amarin, Novartis, and Novo Nordisk; and receiving non-financial support from Abbott, Alexion Pharma, Amgen, Bayer, Boehringer Ingelheim, BMS, Incyte, MSD, and Pfizer. PD reports consulting fees, honoraria for lectures, presentations, or speaker bureaus from Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Menarini, Sanofi, Abbott, MSD, and Bayer; and advisory board participation for Novo Nordisk, Eli Lilly, Menarini, and Boehringer Ingelheim.

Figures

Fig. 1
Fig. 1
Pathophysiology of lower extremity peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM). Other cardiovascular (CV) risk factors may include advanced age, smoking, hypertension, longer duration of diabetes, neuropathy, retinopathy, and prior history of CV disease. Abbreviations CRP, C-reactive protein; IL, interleukin; NO, nitric oxide; PKC, protein kinase C; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-alpha
Fig. 2
Fig. 2
Diagnostic approach for lower extremity peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM). Abbreviations ABI, ankle-brachial index; CTA, computed tomography angiography; MRA, magnetic resonance angiography; TBI, toe-brachial index. *Recommended annual clinical evaluation (medical history, feet inspection, assessing PAD symptoms, monofilament test)
Fig. 3
Fig. 3
Glucose-lowering management approach for lower extremity peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM). Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; BID, twice daily; CKD, chronic kidney disease; GLP-1RA, glucagon-like peptide-1 receptor agonist; HF, heart failure; SGLT2i, sodium-glucose cotransporter-2 inhibitor
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