Morphological Alterations of the Eccrine Sweat Apparatus in Amputated Feet from Diabetes Mellitus Patients

Abstract

Several physiological studies have demonstrated decreased or absent thermoregulatory sweating in the distal legs and feet of diabetes patients. Such hypohidrosis in diabetes patients is believed to be a clinical symptom of autonomic neuropathy. Thus, the present study sought to clarify the pathogenesis of structural alterations of the eccrine sweat apparatus in diabetes patients. For this study, we enrolled 17 patients with diabetic ulcers/gangrene who underwent amputation of the foot. Specimens were obtained 30 mm from the ulcer/gangrene after amputation using a 6-mm trepan, with 12 normal human skin samples obtained from areas adjacent to pigmented nevi or benign skin tumors on the legs or feet to serve as controls. Numbers and morphological abnormalities of eccrine sweat glands and ducts were assessed by light microscopy. The pathogenesis of morphological alterations was examined by electron microscopy and immunoelectron microscopy of type collagen. Rates of disappearance of the lumen, shrunken morphology, and irregular outlines of eccrine sweat glands and ducts were signi cantly higher or more abundant in diabetes patients than in controls P 0.0002 0.0001. Ultrastructurally, we observed prominent thickening of the basement membranes in eccrine sweat glands, admixed cell debris, and narrowing of the lumenal space. The thickened basement membranes resulted in the shrunken morphology and irregular outlines in eccrine sweat glands and ducts. Immunoelectron microscopy showed immunogold labeling for type collagen throughout the thickened basement membrane zone. These morphological alterations of the eccrine sweat apparatus in amputated feet from diabetes patients could be caused by diabetic and/or uremic neuropathy, and at least in part by angiopathy.