Influence of Macrovascular and Microvascular Disease on the Level of Lower-Extremity Amputation in Patients with Type 2 Diabetes

Abstract

Introduction - Peripheral Arterial Disease (PAD) is associated with a high amputation rate in patients with type 2 diabetes (T2DM). However, the relationship between vascular disorders and the level of amputation has been poorly investigated. We examined the impact of microvascular and macrovascular disease on the risk and site of amputation. Our hypothesis was that distal amputations were related to microvascular and proximal amputations to macrovascular disease. Methods - A prospective, monocentric cohort of consecutive T2DM patients (the SURDIAGENE cohort: 1468 patients; 58% men, mean +/- SD age 65+/- 11 years) was followed for a median of 7 years for primary endpoint, global amputation, and secondary endpoints minor amputations (toes and mediotarse leve)l and major amputations (leg and thigh amputation). Microvascular disease was defined as a history of albuminuria or proliferative retinopathy and macrovascular disease as a history of previous coronary revascularization or myocardial infarction or previous carotid revascularization or stroke. History of PAD included previous lower limb revascularization (endovascular or open repair) and previous major amputation. Results - During follow up, 79 patients (5.5%) were amputed: 50 major and 29 minor amputations. History of PAD (HR 5.43 [3.33-8.84]; p<0.0001), Systolic Blood Pressure (SBP) (HR 1.01 [1.00-1.03]; p=0.003) and male sex (HR 4.48 [2.28-8.79]; p<0.0001) were significantly associated with global amputations after multiple stepwise regression model. History of PAD (HR 6.60 [3.61-12.05]; p<0.0001), SBP (HR 1.02 [1.00-1.03]; p=0.006), male sex (HR 3.63 [1.60-8.22]; p=0.002), beta blocker therapy (HR 2.09 [1.16-3.77]; p=0.013), smoking status (HR 2.24 [1.07-4.68]; p=0.031) were associated with major amputations after multiple stepwise regression model. History of PAD (HR 4.04 [1.76-9.26] ; p=0.0009), male sex (HR 5.13 [1.52-12.27] ; p=0.008), proliferative retinopathy (HR 2.60 [1.18-5.72] ; p= 0 .017) and Diastolic Blood Pressure (HR 1.03 [1.00-1.07] were associated with minor amputations after multiple stepwise regression model. History of urinary albumin excretion did not impact global, minor and major amputation. Other atherosclerotic localisations (carotid and coronary artery lesions) had no impact on amputation occurrence regardless of the level of amputation in our model. Minor or major amputation were neither influenced by a surgeon specialty (vascular surgeon vs. orthopedic surgeon; p=0.774) nor surgeon’s experience (senior vs. junior surgeon; p= 0.713). Conclusion - History of PAD was a robust risk factor for amputation regardless the level of amputation in patients with T2DM. Microvascular disease, particularly proliferative retinopathy, predicted minor amputation only. Carotid and/or coronary macrovascular disease did not predict amputation. This study suggests that the risk factors associated with the level amputation (proximal vs distal) should be considered differently in patients with T2DM.