Peripheral vascular bypass in juvenile-onset diabetes mellitus: Are aggressive revascularization attempts justified?

Transcription

1 Peripheral vascular bypass in juvenile-onset diabetes mellitus: Are aggressive revascularization attempts justified? Christopher J. Kwolek, MD, Frank B. Pomposelli, MD, Gary A. Tannenbaum, MD, Colleen M. Brophy, MD, Gary W. Gibbons, MD, David R. Campbell, MD, Dorothy V. Freeman, MD, Arnold Miller, MD, and Frank W. LoGerfo, MD, Boston, 2V1ass. This study was performed to evaluate the results of peripheral vascular reconstruction for arterial occlusive disease in patients with juvenile-onset diabetes mellitus. The results of 67 bypass procedures performed on 6 patients with juvenile-onset diabetes mellitus between Jan. 1, 1984 and Dec. 31, 1989, were reviewed. These patients had a mean age of 44.4 years (range, 29 to 59 years), with an average age of onset of diabetes mellitus of 9.8 years (range, 1 to 19 years). These procedures comprised 5.5% (67 of 1214) of the bypasses performed on diabetic patients during the same time period at a single institution. Fifty-four of 67 (91%) procedures were performed for limb salvage. Fifty-four (81%) procedures were primary infrainguinal bypasses with saphenous vein (femoropopliteal 19, femorodistal or popliteal-distal 35). Six procedures (9%) were revision procedures, four (6%) were in-flow procedures, and three (4%) were infrainguinal procedures with polytetrafluoroethylene. Thirty-day morbidity and mortality rates were 31% and %, respectively. Actuarial patency and limb salvage rates of the primary vein graft group were 66.% (-+ 1.7) and 83.4% (-+ 8.%), respectively, at 24 months. Cumulative survival of the entire group at 2 years was 84.1%. Although follow-up in this study is relatively short (24 months), the results suggest that the outcome of vascular reconstruction in patients with juvenile-onset diabetes mellitus is acceptable when compared with procedures performed in adult-onset diabetic and nondiabetic populations. The presence of juvenile-onset diabetes mellitus should not diminish the vascular surgeon's expectations of a successful outcome when considering lower extremity revascularization in these patients. (J VASC SURG 1992;15: ) Diabetes mellitus is found in only 2% of the population, yet accounts for 5% to 66% of the patients undergoing lower extremity amputation in the United States each year. 1'2 Because of the high monetary and psychologic costs of primary amputation in these patients, 3 and the increasing success of distal arterial reconstruction to the tibial, peroneal, and pedal vessels being reported by various groups, 4 an increasingly optimistic outlook has been advocated when evaluating these patients for peripheral vascular reconstruction. The success of these reports is based on a combination of comprehensive local foot care including broad-spectrum antibiotic From the Division of Vascular Surgery, New England Deaconess Hospital, Harvard Medical School. Presented at the Forty-fifth Annual Meeting of the Society for Vascular Surgery, Boston, Mass., June 4-5, Reprint requests: Frank B. Pomposelli, MD, I1 Francis St., Suite 9C, Boston, MA /6/ therapy, local debridement, and resting (non-weight bearing) of the involved extremity, in addition to an aggressive approach to distal revascularization in those patients with limb-threatening ischemia, s,6 On the other hand, because of the increased incidence of concomittant cerebral, coronary, renal, and peripheral vascular disease along with a decreased median survival in these patients, 7,s attempts have been made to identify those patients in whom arterial reconstruction is not likely to be successful. Several authors have evaluated the results of vascular bypass in patients with end-stage renal disease, who were thought to be at high risk because of their diffuse systemic arterial involvement, the extensive calcification of their vessels, and the large percentage of diabetic patients in this population?,9 Others have reviewed the results of vascular reconstructive procedures in patients under the age of 5 years, based on anecdotal reports indicating poorer results

2 Volume 15 Number 2 February 199:2 Peripheral vascular bypass in patients with juvenile-onset diabetes 395 in this age group. 1 In neither group has a consensus regarding the suitability of these patients for peripheral vascular bypass been reached. A patient population that combines the risk factors of both the above-mentioned groups, are those individuals with onset of insulin-dependent diabetes meuitus before the age of 2 years, so-called juvenile-onset diabetes mellitus (JODM). The incidence of diabetes mellims is bimodal, with peaks occurring at puberty, often referred to as JODM, and in the sixth decade of life, referred to as adult-onset diabetes mellitus (AODM). Approximately 95% of patients with onset of diabetes mellitus before the age of 2 years are dependent on insulin, yet they comprise only 1% to 2% of the population with known overt diabetes. 8 Differences in the clinical, biochemical, autoimmune, and genetic features of these two groups, such as the presence of insulin and pancreatic islet cell autoantibodies, elevation of serum C-peptide concentrations, and heterozygosity for the human leucocyte antigen (HLA) specificity DR3/DR4, and differences in the course of the disease have been previously described. :x'~2 The purpose of this study was to determine whether the reported differences between these two groups extends to the outcome of peripheral vascular reconstructive procedures performed in patients with JODM. PATIENTS AND METHODS We reviewed the results of 67 bypass procedures performed on 6 patients with JODM during the 5-year period between January 1984 and December Patients with JODM were defined as those with onset of diabetes before the age of 2 years and who were dependent on insulin during the entire course of their diabetes. These 67 procedures comprised 4% of the 1632 bypasses performed at the New England Deaconess Hospital during the same 5-year time period and 5.5% of the 1214 bypasses performed on diabetic patients. The preoperative demographic characteristics of these patients and their preoperative risk factors are summarized in Table I. Nearly all of the patients had previously documented neuropathy and retinopathy, and approximately one half had a history of renal failure defined as a serum creatinine greater than 2.1 mg/dl. At the time of bypass, 21 patients had previously required dialysis, and 14 of these patients had received a kidney transplant, i3 of which were still functioning and one that had been previously removed. Only one quarter of the patients had no previous smoking history. Preoperative infection, in Table I. Demographic breakdown of patients with juvenile-onset diabetes Total patients 6 Men 3 i Women 29 Mean age (range) 44.4 yrs (29-59) Mean age at onset of diabetes 9.8 yrs (1-19) Mean duration of diabetes (range) 34.6 yrs (2-52) Preoperative Risk Factors IDDM 6 (1%) Hypertension 27 (45%) Neuropathy 6 (i%) Retinopathy 55 (92%) Renal Failure 27 (45%) Dialysis 21 (35%) Previous kidney transplant 14 (23%) Smoking Current Previous 26 '~(65%) 13 j Never 15 (25%) Unknown 6 IDDM, Insulin-dependent diabetes mellims. addition to ischemia, was documented in 69% of the patients, with 14 (2%) patients requiring preoperative debridement in addition to treatment with broad spectrum intravenous antibiotics. A summary of the previous vascular procedures performed on these patients and indications for surgery are listed in Table II, with 91% of the procedures being performed for limb salvage. Eighty-one percent of the 67 procedures performed were primary infrainguinal bypasses with saphenous vein, 4% were primary- above-knee popliteal bypasses with polytetrafluoroethylene (PTFE), 6% were primary inflow procedures, and 9% were reoperations or revisions of previously placed bypass grafts. The breakdown of these procedures according to inflow vessel, outflow vessel, and type of conduit used are provided in Tables III and IV. All patients discharged with patent grafts were seen at 2 weeks, then every 3 months during the first year, and at 6-month intervals during the subsequent years. Graft patency was determined by the presence of a palpable pulse in the graft and by Doppler derived pressures. Primary and secondal T graft patency, fimb salvage, and patient survival were analyzed by the life-table method with use of criteria established by the Joint Council of the International Society for Cardiovascular Surgery/ Society for Vascular Surgery. :3 Because of the small number of patients in the primary procedure with prosthetic material (PTFE/Dacron) group and the reoperation/revision group, the results of these bypasses were only analyzed for 3-day graft patency.

3 396 Kwolek et al. Jo~nalof VASCULAR SURGERY Table II. Previous procedures and operative indications Previous Amputation Major 9 (13%) Minor 23 (34%) Previous Vascular Procedures PTCA/CABG 4 Arteriovenous fistula 1 Contralateral bypass graft 8 Ipsilateral bypass graft 6 Ipsilateral inflow procedure 8 Other* 6 Indications for Surgery Threatened limb 61 (91%) Rest pain 4 Nonhealing ulcer 31 Gangrene 24 Failed amputation 2 Claudication 6 (9%) PTCA/CABG, Percutaneous transluminal coronary angioplasty/coronary artery bypass grafting. * 1-radial artery bypass, 2-contralateral angioplasty, 3-contralateral sympathectomy. Table III. Primary procedures (vein graft) Total cases 54 Femoropopliteal (AK) 1 Femoropopliteal (BK) 9 Femorodistal 24 Popliteal-distal 11 Conduit Reversed 25 Nonreversed 6 In sire 22 Composite 1 RESULTS The perioperative mortality rate at 3 days for the entire group of patients was %. The perioperative complication rate was 31% for the entire group, with an overall cardiovascular complication rate of 7.5 % and a rate of 4.7% when excluding those patients who underwent an inflow procedure (Table V). Seventeen of the 54 (31%) primary infrainguinal bypass grafts performed with saphenous vein failed during the course of the study, resulting in nine major limb amputations (53%). Five of the failed grafts were successfully revised (29%) and the limbs saved. Three of the graft failures (18%) were not revised, but did not result in limb loss. Actuarial life-table analysis of primary and secondary graft patency and limb salvage for the 54 patients undergoing primary infrainguinal bypass with saphenous vein were 66% (+ 1.7%), 75.4% (- 9.7%), and 83.4% (+ 8%), respectively, at 24 months (Figs. 1, 2, and 3). The 3-day patency for the group of patients undergoing primary procedures with PTFE or Dacron was Table IV. Primary procedures (PTFE/Dacron) Total 7 Aorta-bifem 1 Aortabifem/fem-pop (PTFE) 1 Aortabifem/fem-pop (RSV) 1 Axillobifemoral 1 Femoropopliteal 2 Femoropopliteal/pop-distal (RSV) 1 Reoperatious/revisions Total 6 Iliac-popliteal (PTFE) 1 Femoropopfiteal (PTFE) 1 Femoro-post. tibial (ISSV) 1 Popliteal-DP (RSV) 1 Vein patch angio of previous fempop 1 (sv) Vein patch angio of previous fern-pop 1 (SV)/jump graft to DP (NRAV) RSV, Reversed saphenous vein; ISSV, in situ saphenous vein; SV, saphenous vein; NRAV, nonreversed arm vein; DP, dorsal pedal. 1%. The 3-day patency was 67% for the group of patients undergoing reoperative/revision procedures. Actuarial patient survival was 84% at 24 months (Fig. 4). In addition to vascular reconstruction, 11 of 54 (16%) patients required a postoperative minor amputation or dcbridement to achieve a healed foot. No major amputations were performed in patients who maintained a patent graft. Seven of the nine patients who ultimately lost their limb after graft failure had a history of chronic renal failure. DISCUSSION The combination of ischemia, infection, and neuropathy in the diabetic patient with a foot problem leads to a complex set of events that can result in destruction of the foot and may explain the high incidence of major limb amputation in these patients. In recent years, several centers, including our own, have demonstrated that an aggressive coordinated approach to these problems can reduce the likelihood of this devastating complication. 14 One of the greatest obstacles to appropriate treatment of diabetic foot problems has been the undue pessimism many clinicians have toward these patients, because of the misconception that they have an untreatable occlusive lesion in the microcirculation (i.e., small vessel disease). This concept originated more than 3 years ago from a single retrospective histologic study of amputated limbs from patients with diabetes mellims, and persists despite several subsequent prospective histologic and anatomic studies that found no evidence of a microvascular occlusive lesion specific to diabetes) s,~6

4 Volume 15 Number 2 February 199:2 Peripheral vascular bypass in patients with juvenile-omet diabetes 397 (54) 1-9 >,. o z la,i I-- O.. ILl > I I I I (33) (3) (29) (25) (24) T t I (21) (19) (17) (13),,--I 5: 4 to i FOLLOWUP IN MONTHS Fig. 1. Primary patency of primary infrainguinal bypass grafts with saphenous vein. 24 The results of the present study support the concept that small vessel disease does not exist in the diabetic lower extremity. Persons with IODM comprise a small number of those patients with diabetes undergoing vascular reconstruction (5.5% in this series). However, this subgroup of patients has a very high incidence of both ocular and renal microangiopathy. In this series 92% of the patients had known retinopathy and 45% had renal failure, in many dialysis or renal transplantation or both were required. If small vessel disease occurs in the lower extremities of diabetic patients and significantly contributes to the problem of peripheral ischemia, then this group would be most at risk for its presence, and vascular reconstruction should be expected to be largely unsuccessful. However, graft patency and limb salvage rates in this series were acceptable when compared with other series of peripheral vascular bypass for ischemia in both AODM and nondiabetic populations. 4,1r,18 Moreover, no patients in this study lost a limb while their graft remained patent, whereas graft failure that could not be revised led to major amputation in 53% of the patients. These results suggest that occlusive disease in the large vessels is the principal cause for ischemia-related limb loss in these patients. Although the lesions leading to ischemic tissue Table V. Perioperative morbidity and mortality for all 67 procedures Perioperative mortality Perioperative complications 21 (31%) Infection Wound infection 3 Abscess 1 Urinary tract infection 2 Sepsis 1 C. Dificile Enterocolitis 1 Cardiovascular Angina/ischemia 3 Myocardial infarction 2 Hemorrhage Retinal hemorrhage 1 Wound hematoma 2 Other Ileus 2 Urinary retention 1 Uncontrollable diabetes mellims 1 Renal insufficiency 1 loss in patients with IODM appear to be similar to those in patients with AODM and nondiabetics, several differences were uncovered in the present study. There were an even number of male and female patients who required bypasses in this study, different from the 2:1 male/female ratio reported in two

5 398 Kwolek et al. Journal of VASCULAR SURGERY (54) 1 ~~._~ p- to z LU k.- O. LU I--,.J 9O 8 7O 6 5' 4O 3O (45) (41) I I I I I I I I I I I I I I I (35) (32) (32) (28) (27) (25) (22) (2) (15) 2O FOLLOWUP IN MONTHS Fig. 2. Secondary patency of primary infrainguinal bypass grafts with saphenous vein. 1.1,1 t,.9._1 (54) 1 9 I 8O - ~[ (4) (36) 7O 6 5 T (36) (31) (3) (28) (25) (23) (18) m _1 4O 3O 2O FOLLOWUP IN MONTHS Fig. 3. Limb salvage rates for primary infrainguinal bypass grafts with saphenous vein. recent articles on vascular bypass procedures performed on diabetic patients from this same institution. 4,~4 This is also consistent with the observation of Beach and Strandness 12 who previously reported that the incidence of arteriosclerosis obliterans is higher in men than in women with non-insulin-dependent diabetes, but that a 1:1 male/female ratio is seen in patients with insulin-dependent diabetes. In addition, the mean age of the patients in this study was 44 years, much lower than the mean age of 68 years

6 Volume 15 Number 2 February 1992 Peripheral vascular bypass in patients with juvenile-onset diabetes 399 (6),,,,l > 1 t (57) *1 8 7 g (53) /5/ I I! I I T (47) (47) I I I I I (41 ) (4) (38) (34) (31 ) (26) n" :D 6 I',a.I >_ j,..,_1.'.d,,~ :D ; FOLLOWUP IN MONTHS Fig. 4. Cumulative actuarial survival rate for all patients. reported by Rosenblatt et al. 4 in a review of vein graft reconstruction of the lower extremity in diabetic and nondiabetic patients. The overall complication rate of 31% in this series is high when compared with other series of vascular bypass procedures. 4a4'17 However, given the high incidence of comorbid disease seen in these patients, the low incidence of serious cardiovascular complications, mad the low perioperative mortality rate, the risk appears to be within an acceptable range. The 2-year cumulative survival rate of 84% in this young group of patients seems low. However, recent data from a long-term study at the Joslin Diabetes Center of 292 patients with JODM revealed that one half of the patients were dead by the age of 54 years, and their median survival was decreased by 25 years when compared with the general population. 2 Survival is not adversely affected by the presence of JODM during the first 25 years of life. The mortality rate markedly increases beginning at the age of 35 years, with more than one half of the fatalities related to complications of either coronary artery disease or renal failure. 8 In addition, the incidence of morbidity caused by other complications increases with time. Approximal:ely 4% of patients with JODM will have documented severe retinopathy and nephropathy within 3 years of their diagnosis. 7 This excess of deaths is also noted in patients with AODM, but to a much lesser degree. An increased mortality rate is not noted in AODM until the age of 5 years. Median survival is diminished by only 12 years for women and 5 years for men with AODM by the age of 65 years. 2 The large number of patients requiring major amputation after failure of their bypass grafts in this study attests to the severity of the peripheral vascular disease in this group of patients. Because of the small overall number of patients in this study, no single preoperative risk factor could be identified as a predictor of poor outcome with respect to graft patency and limb salvage. However, the presence of complete renal failure requiring either hemodialysis or kidney transplantation was associated with a greater incidence of limb loss after graft failure and a lower incidence of successful graft revision. These results suggest that patients with a history of renal failure have more advanced degrees of arterial insufficiency when admitted for bypass surgery and thus tolerate graft failure poorly. Intervention for ischemic complications should be undertaken promptly in this group of patients, and on the basis of these findings, development of a policy of close postoperative follow-up to detect early signs of graft dysfunction may be most beneficial in this group of patients.

7 4 Kwolek et al. Journal of VASCULAR SURGERY In summary, patients with JODM have onset of their ischemic complications and require peripheral bypass surgery at a much younger age than their counterparts with AODM or other nondiabetic patients. Although the follow-up in this series is relatively short, and the outcome was less successful than the 8% to 85% limb salvage/patency rates reported in other large series of AODM and nondiabetic populations, the results of peripheral vascular bypass in patients with JODM are acceptable and support the concept that small vessel disease of the lower extremity does not play a significant role in these patients. It should be noted, however, that those patients with a previous history of complete renal failure have a very high rate of major amputation if their bypass grafts fail. Nevertheless, we think that the presence of JODM should not diminish the vascular surgeon's expectations of a successful outcome when considering lower extremity revascularization in this group of patients. REFERENCES 1. Ger R. Prevention of major amputations in the diabetic patient. Arch Surg 1985;12: Stemmer EA. Influence of diabetes meuitus on the patterns of vascular occlusive disease. In: Moore WS, ed. Vascular surgery-a comprehensive review. 2nd ed. Orlando: Grune & Stratton, 1986: Edwards IA, Taylor LM, Porter JM. Limb salvage in end-stage renal disease. Arch Surg 1988;123: Rosenblatt MS, Sidawy AN, Paniszyn CC, LoGerfo FW. Results of vein graft reconstruction of the lower extremity in diabetic and nondiabetic patients. Surg Gynecol Obstet I99;171: Gibbons GW. The diabetic foot: amputations and drainage of infection. J VASC SURG 1987;5: Mclntyre KE. Control of infection in the diabetic foot: the rule of microbiology, immunopathology, antibiotics, and guillotine amputation. J VASC SURG 1987;5: Lestradet H, Papoz L, Hellouin De Menibus CL, et al. Long-term study of mortality and vascular complications in juvenile-onset (type I) diabetes. Diabetes 1981;3: Krolewski AS, Warram JH, Christlieb AR. Onset, course, complications and prognosis of diabetes mellims. In: Marble A, ed. Ioslins: diabetes mellitus. 12th ed. Philadelphia: Lea and Febiger, 1985: Harrington EB, Harrington ME, Schanzer H, Haimov M. End-stage renal disease-is infrainguinal limb revascularization justified? J VASC SURG 199;12: N-Hsiang Y, Hildebrand HD. Results of vascular surgery in younger versus older patients. Am J Surg 1989;157: li. Karjalainen J, Salmela P, Ilonen J, et al. A comparison of childhood and adult type I diabetes meuitus. N Engl J Med 1989;32: I2. Beach KW, Strandness DE. Arteriosclerosis obliterans and associated risk factors in insulin-dependent and non-insulindependent diabetes. Diabetes 198;29: Rutherford RB, Flanigan DP, Gupta SK, et al. Suggested standards for reports dealing with lower extremity ischemia. J VASC SURG 1986;4: Pomposelli FB, lepsen SJ, Gibbons GW, et al. Efficacy of dorsal pedal bypass for limb salvage in diabetic patients: short term observations, l VAsc SURG 199;11: Strandness DE, Priest RE, Gibbons GE. Combined clinical and pathologic study of diabetic and nondiabetic peripheral arterial disease. Diabetes 1964;13: ConradMC. Large and small artery occlusion in diabetics and nondiabetics with severe vascular disease. Circulation 1967; 36: Hurley JJ, Auer AI, Hershey FB, et al. Distal arterial reconstruction: patency and limb salvage in diabetics. J VASC SURG 1987;5: I8. Reichle FA, Rankin KP, Tyson RR, et al. Long-term results of 474 arterial reconstructions for severely ischemic limbs: a fourteen-year followup. Surgery 1979;35:93-7. Submitted June 1, 1991; accepted Aug. 15, DISCUSSION Dr. Eugene Strandness (Seattle, Wash.). This interesting report again highlights the important differences between the patient with type I and type II diabetes. The patient with type I requires insulin to remain alive, which is not the case in type II. I would like to ask the authors this question: Are you 1% sure that all these patients required insulin for maintenance of life, because this is an important issue? The differences between the two groups of patients have been reviewed, but I would simply like to reiterate and emphasize the important facts concerning these two groups of patients. The overall prevalence of occlusive arterial disease is lower in patients with type I diabetes than in those with type II. This is due to the fact that they have not lived long enough to develop the problem. The mean age of time of death is low in type I diabetics. They are most often dead by the age of 5 years. This is in contrast to type II diabetics who will survive much longer. The mean age of the time of death in our studies was 72 years. There is a very high incidence of severe retinopathy and renal failure in the Type I diabetic. The renal failure greatly complicates management of their disease and also contributes to their early death. The microangiopathy of type I diabetics in the eye and the kidney cannot be equated with similar findings in the

8 Volume 15 Number 2 February 1992 Peripheral vasc~tlar bypass in patients with juvenile-onset diabetes 41 lower limbs. This reiterates the fact that diabetic small vessel disease should not be considered part of the surgeon's vocabulary when referring to these patients. It is amazing that even today every medical student and many residents continue to be: taught that the high incidence of limb loss from diabetes is a result of this small vessel disease problem. Although many nonsurgeons consider the tibialperoneal arteries as small vessels, they are not. They are medium size arteries and can be bypassed when they are diseased with a good chance of success. I have a fe, w questions for the authors. Number one, a high prevalence of previous amputations existed. There were nine major amputations, i3% and 23% or 34% minor amputations. Were the minor amputations a result of the development of neuropathic ulcers and their complications? Number two, were there any particular combina- ~,ions that had a poorer outlook? For example, did the toresence of a deep space infection or involvement of tendon and bone account for some of the failures that led to amputation? Finally, what about the timing of the operation, particularly when there is superimposed infection? Dr. Christopher Kwolek. Dr. Strandess first asked if we are certain that all the patients in this study are truly insulin-dependent diabetics. The definition we chose was a clinical one based on discussions with our diabetologists at the Joslin Diabetes Center. We included only patients who had onset of diabetes before the age of 2 years and who were insulin-dependent during the entire course of their diabetes. Serum insulin levels were not obtained in this retrospective study; however, our diabetologists think that our clinical criteria are restrictive enough to exclude any patients with AODM. This patient group of only 6 patients over 5 years is quite small when compared with the large number of diabetic patients that we treat at our hospital. Most minor amputations performed before the bypass were due to complications of neuropathy. Nearly 1% of the patients in this study had both neuropathy and retinopathy documented before their bypass procedure. It is important to emphasize that concomitant treatment of neuropathy and secondary infection by a combination of broad-spectlmm antibiotics, aggressive incision, and drainage and/or debridement, and resting of the involved extremity are important in addition to correcting vascular insufficiency, to ultimately achieve foot salvage. Because of the small numbers in this study, we were not able to identify any single risk factor or combination of risk factors that predicted a poor outcome. However, those patients with chronic renal failure who were dependent on dialysis who lost their grafts accounted for seven of the nine amputations seen in this group. The overall graft patency rate in this small subgroup of patients was similar to the overall group, approximately 67%. However, loss of graft resulted in a higher rate of amputation, suggesting that patients with chronic renal failure present with their vascular disease in a later and more critical phase. With respect to the question about timing of our operative procedures with superimposed infection, it is important that active infection has been completely controlled before undertaking a vascular reconstruction. This often requires broad-spectrum intravenous antibiotics and aggressive incision and drainage and/or bedside or operarive debridement, including partial open forefoot amputation as necessary. Clinical signs of resolving infection include resolution of fever, leukocytosis, and return of good glucose control, along with resolution of edema, cellulitis, and lymphangitis. Once this has occurred, revascularization should be undertaken promptly. Longer delays may result in further tissue loss and/or recurrent foot infection. Dr. Malcolm Perry (Nashville, Tenn.). I have a question. Are you able to separate those who have a neuropathy and a traumatic lesion from those who appear with ischemic gangrene or ischemic necrosis? Can you detect in that group a different natural history? We have been led to believe that they are quite different. Dr. Kwolek. Dr. Perry, the most important way to differentiate clinically those patients with a foot lesion caused purely by neuropathy, as opposed to those with lesions caused by ischemia, is the status of foot pulses. The cause for most foot ulcerations in our diabetic patients is peripheral neuropathy; however, those without ischemia will usually have strongly palpable foot pulses and will respond to the usual conservative measures. Those with absent foot pulses are likely to have arterial insufficiency and, if they are not responding promptly to conservative measures, should undergo arteriography and aggressive revascularization attempts as indicated.