Large and small peripheral arterial disease in persons with type 2 diabetes

Abstract Background We sought to investigate disease incidence trends and risk factor associations for large- and small-vessel peripheral arterial complications in persons with type 2 diabetes (T2D) compared with matched controls from the general population. Methods This study included persons with T2D entered into the Swedish National Diabetes Register 2001-2019 and controls matched on age, sex and county of residence. Incident diagnoses comprised extracranial large artery cerebrovascular disease (ELAD), aortic aneurysm (AA), aortic dissection (AD) and large- and small-vessel peripheral artery disease (LV-PAD; SV-PAD) of the lower extremities. Standardized incidence rates and Cox regression were used for analyses. Results The study comprises 655,250 persons with T2D; average age 64.2; 43.8% women. Among persons with T2D, the incidence rates per 100.000 person years for each peripheral arterial disease diagnosis changed between 2001 and 2019 as follows: ELAD 170.0 to 84.9; AA 40.6 to 69.2; AD 9.3 to 5.6; LV-PAD from 338.8 to 190.8; and SV-PAD from 309.8 to 226.8. Baseline hemoglobin A1c (HbA1c), systolic blood pressure (SBP), smoking status and lipid levels were independently associated with all outcomes in the T2D cohort. Within the cohort with T2D, the risk for ELAD and LV-PAD increased in a stepwise fashion for each risk factor not within target. Excess risk for peripheral arterial complications in the entire cohort for persons with T2D were as follows: ELAD HR 1.69 (95% CI, 1.65-1.73), AA 0.89 (95% CI, 0.87-0.92), AD 0.51 (95% CI, 0.46-0.57) and LV-PAD 2.59 (95% CI, 2.55-2.64). Conclusions The incidence of peripheral arterial complications has declined significantly among persons with T2D, with the exception of AA. HbA1c, smoking and blood pressure demonstrated greatest relative contribution for outcomes and lower levels of cardiometabolic risk factors are associated with reduced relative risk of outcomes. Clinical Perspective What is new? This nationwide registry data show that individuals with T2D and the general population displayed large reductions in rates of atherosclerotic peripheral arterial complications and SV-PAD, whereas aortic aneurysms increased in T2D and aortic dissections remained unchanged. Overall, excess risk for atherosclerotic peripheral arterial complications is elevated among individuals T2D, but diabetes was associated with lower risk of aortic complications. Patients with T2D versus controls with no cardiometabolic risk factor (i.e., HbA1c, SBP/DBP, LDL-C, smoking and eGFR) beyond target displayed a significant lower risk of peripheral arterial complications, with the exception of LV-PAD were T2D was still associated with increased risk. What are the clinical implications? To achieve the most substantial relative risk reduction for all peripheral arterial complications, it is crucial to focus on improving glycated hemoglobin levels, blood pressure control, and smoking cessation. SV-PAD has emerged as the most common complication affecting the peripheral arteries. Relative importance of these risk factors differs between cardiovascular disease and peripheral arterial complications, with glycated hemoglobin levels assuming a more significant role in the latter. Regarding risk factors, maintaining glycated hemoglobin and systolic blood pressure levels below the recommended therapeutic targets significantly reduces the risk of atherothrombotic peripheral arterial complications. Conversely, increasing levels of these factors were associated with a reduced risk of aortic complications.