Etiologic Considerations in Peripheral Vascular Diseases of the Lower Extremity with Special Reference to Diabetes Mellitus

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Abstract
A histopathologic and immunopathologic study of changes in small vessels has been carried out on 168 amputated lower extremities. No difference was found in respect to the frequency of thrombotic or atheromatous lesions among the various clinical disease categories necessitating amputation. An increased frequency of inflammatory lesions of small vessels was found only in cases of osteomyelitis. The frequency of hemodynamic lesions was highest in nondiabetic subjects with arteriosclerosis, and second highest in diabetic subjects with arteriosclerosis, followed by thromboangiitis obliterans. Proliferative endothelial lesions were encountered most frequently in diabetes with arteriosclerosis, in osteogenic sarcoma, and in osteomyelitis. Such proliferative lesions were encountered in 80 per cent of diabetic subjects and in 20 per cent of nondiabetic individuals. Fluorescent insulin binding by small vessels was found in 70 per cent of diabetic subjects with proliferative vascular lesions and in only 30 per cent of diabetic individuals without this proliferative microangiopathy. Such insulin binding was observed in 54 per cent of diabetic subjects and in only about 15 per cent of nondiabetic patients. The binding of fluorescent rabbit antihuman globulin was observed in 56 per cent of diabetic subjects and in 22 per cent of nondiabetic patients. These findings are discussed in relation to the thesis that there may be diseases of immune origin primarily involving small peripheral vessels. The peripheral vascular disease of diabetes is particularly stressed here because it is probably the most common form of such disease of immune origin. Such pathologic processes in small vessels may secondarily involve large cognate system arteries, either by creating an increased peripheral resistance to the flow of blood or when lesions involve the vasa vasorum, there may be impairment of local nutrition. Either or both of these phenomena could intensify the development of arteriosclerosis of large trunk arteries. Although no attempt has been made here to justify or negate the existence of thromboangiitis obliterans as a disease entity, it has been pointed out that at least some cases with this diagnosis may have a similar immune origin.