Jessie H. Ahroni

The Independent Contributions of Diabetic Neuropathy and Vasculopathy in Foot Ulceration: How Great Are the Risks?

OBJECTIVE To describe the relative contributions of neurological and vascular abnormalities to the overall risk of diabetic foot ulceration. RESEARCH DESIGN AND METHODS A case-control study of diabetic veterans from the Seattle Veterans Affairs Medical Center was conducted using data collected from 46 patients with diabetic foot ulcers and 322 control subjects. Neuropathy was determined by vibratory, monofilament, and tendon reflex testing. Macro-vascular disease was measured by ankle-arm blood pressure index, and cutaneous perfusion was measured by transcutaneous oxygen tension (TcPO2) on the dorsal foot. A multi variate logistic regression model was used to adjust for confounding variables and to calculate the odds ratios (ORs) for each independent risk factor. RESULTS Three variables were significant independent predictors of foot ulceration: absence of Achilles tendon reflexes (adjusted OR 6.48, 95% confidence interval [CI] 2.37–18.06), insensate to the 5.07 monofilament (adjusted OR 18.42, 95% CI 3.83–88.47), and TcPO2 <30 mmHg (adjusted OR 57.87, 95% CI 5.08–658.96). Absent vibratory sensation and low ankle-arm blood pressure index were not significant independent risk factors. CONCLUSIONS Both neuropathy and vasculopathy are strong independent risk factors for the development of diabetic foot ulcers. In our model, the strongest risk factor is impaired cutaneous oxygenation. However, in the clinical setting, sensory examination with a 5.07 monofilament probably remains the single most practical measure of risk assessment.

Prediction of Diabetic Foot Ulcer Occurrence Using Commonly Available Clinical Information: The Seattle Diabetic Foot Study

OBJECTIVE—The ability of readily available clinical information to predict the occurrence of diabetic foot ulcer has not been extensively studied. We conducted a prospective study of the individual and combined effects of commonly available clinical information in the prediction of diabetic foot ulcer occurrence. RESEARCH DESIGN AND METHODS—We followed 1,285 diabetic veterans without foot ulcer for this outcome with annual clinical evaluations and quarterly mailed questionnaires to identify foot problems. At baseline we assessed age; race; weight; current smoking; diabetes duration and treatment; HbA1c (A1C); visual acuity; history of laser photocoagulation treatment, foot ulcer, and amputation; foot shape; claudication; foot insensitivity to the 10-g monofilament; foot callus; pedal edema; hallux limitus; tinea pedis; and onychomycosis. Cox proportional hazards modeling was used with backwards stepwise elimination to develop a prediction model for the first foot ulcer occurrence after the baseline examination. RESULTS—At baseline, subjects were 62.4 years of age on average and 98% male. Mean follow-up duration was 3.38 years, during which time 216 foot ulcers occurred, for an incidence of 5.0/100 person-years. Significant predictors (P ≤ 0.05) of foot ulcer in the final model (hazard ratio, 95% CI) included A1C (1.10, 1.06–1.15), impaired vision (1.48, 1.00–2.18), prior foot ulcer (2.18, 1.61–2.95), prior amputation (2.57, 1.60–4.12), monofilament insensitivity (2.03, 1.50–2.76), tinea pedis (0.73, 0.54–0.98), and onychomycosis (1.58, 1.16–2.16). Area under the receiver operating characteristic curve was 0.81 at 1 year and 0.76 at 5 years. CONCLUSIONS—Readily available clinical information has substantial predictive power for the development of diabetic foot ulcer and may help in accurately targeting persons at high risk of this outcome for preventive interventions.

Risk Factors for Diabetic Peripheral Sensory Neuropathy Results of the Seattle Prospective Diabetic Foot Study

OBJECTIVE To identify risk factors for diabetic lower-extremity peripheral sensory neuropathy prospectively in a cohort of U.S. veterans with diabetes. RESEARCH DESIGN AND METHODS General medicine clinic outpatients with diabetes were followed prospectively for the development of insensitivity to the 5.07 monofilament on the foot. RESULTS Of 775 subjects, 388 (50%) had neuropathy at baseline. Of the 387 subjects without neuropathy at baseline, 288 were followed up, and of these, 58 (20%) developed neuropathy. Multivariate logistic regression modeling of prevalent neuropathy controlling for sex and race revealed independent and significant associations with age, duration of diabetes, glycohemoglobin level, height, history of lower-extremity ulceration, callus, and edema; an independent and inverse correlation was noted with ankle-arm index. Risk factors for incident neuropathy in multivariate logistic regression included age, baseline glycohemoglobin level, height, history of ulcer, and CAGE screening instrument alcohol score; current smoking and albumin level were inversely associated with risk. CONCLUSIONS Poorer glycemic control increases the risk of neuropathy and is amenable to intervention. Height and age directly increase risk of neuropathy and may help identify patients at risk. A proportion of neuropathy in diabetic veterans is probably due to or worsened by alcohol ingestion. Neuropathy was less common in current smokers than subjects not currently smoking.

Chronology and Determinants of Tissue Repair in Diabetic Lower-Extremity Ulcers

The natural history of tissue repair and the critical determinants of faulty healing of diabetic ulcers remain obscure despite recent advances in our knowledge of the cellular physiology of normal cutaneous healing. To characterize the chronology and identify important factors affecting healing, we applied an objective method to quantify the rate of wound healing of full-thickness lower-extremity ulcers in 46 diabetic outpatients who received local wound care under a standardized clinical protocol. The initial ulcer healing rate, eventual status of tissue repair, and definitive clinical outcome were not significantly associated with age; diabetes type, duration, or treatment; level or change in glycosylated hemoglobin; current smoking; presence of sensory neuropathy; ulcer location or class; initial infection; or frequency of recurrent infections. However, direct measures of local cutaneous perfusion, estimated by periwound measurements of transcutaneous O2 tension (TcPo2) and transcutaneous CO2 tension (TcPco2), were significantly associated with the initial rate of tissue repair (P = 0.003 and 0.005, respectively). The strong prediction of early healing by these parameters of local skin perfusion was independent from the effects of segmental Doppler arterial blood pressure at the dorsalis pedis, although eventual ulcer reepithelialization was significantly related to foot blood pressure and periwound TcPo2 and TcPco2. We conclude that periwound cutaneous perfusion is the critical physiological determinant of diabetic ulcer healing, indicating a 39-fold increased risk of early healing failure when the average periwound TcPo2 is <20 mmHg.

Reliability of F-Scan In-Shoe Measurements of Plantar Pressure

Research by our group and others indicates that many amputations of the lower limb occur after foot ulceration in patients with diabetes. It has been proposed that diabetic foot ulcers are mainly caused by repetitive trauma in areas of high plantar pressure during walking. Recent technology permits in-shoe measurement of plantar pressure. We assessed the reliability of the F-Scan in-shoe system for measurement of plantar pressure (Tekscan Inc., Boston, MA) in 51 subjects from a cohort of 977 diabetic veterans enrolled in a prospective study of risk factors for foot ulceration and amputation (the Seattle Diabetic Foot Study). Subjects were tested twice, wearing their own shoes. We used the coefficient of variation (CV) and the intraclass correlation coefficient (ICC) to estimate the reliability of F-Scan measurements of pressure. Peak pressure over the metatarsal heads proved to have the best indices of reliability, with CVs of 0.150 and 0.155, and ICCs of 0.755 and 0.751. Coefficients of variation for the heel, whole foot, and hallux ranged from 0.148 to 0.240, with ICCs ranging from 0.493 to 0.832. By published standards, peak pressures over the metatarsal heads and right hallux met the criteria for excellent reliability. Our ICCs for high pressures under the foot, heel, metatarsal heads, and hallux, and for peak pressures under the heel and left hallux represented fair-to-good reliability. No F-Scan plantar measurements could be judged by these criteria as having poor reliability. This clinical study found that for elderly patients with diabetes who were wearing their own shoes and were tested on two different days with different insoles, the F-Scan insole system was generally reliable for measurements of high pressure and peak pressure.

Laparoscopic Adjustable Gastric Banding: Weight Loss, Co-morbidities, Medication Usage and Quality of Life at One Year

Background: The objective of this study was to determine the weight loss, changes in co-morbidities, medication usage and general health status at 1 year after laparoscopic adjustable gastric banding (LAGB). Methods: Prospective data were obtained from all subjects undergoing LAGB. These measurements included a medical history and review of systems, medications, height and weight and the SF-36 general health survey. Patients were seen for band adjustments as needed throughout the year. At the 1-year follow-up visit, patients were weighed and interviewed about the status of their health conditions and their current medications, and the SF-36 was repeated. Results: Between November 2002 and November 2003, 195 patients had LAGB. The majority of subjects were female (82.8%), married (65.1%), and white (94.9%). Complications occurred in 18 subjects (9.2%). These included 3 slipped bands (1.5%), 4 port problems (2.1%), 8 patients with temporary stoma occlusion (4.1%), 1 explantation (0.5%), and 1 mortality (0.5%). Mean BMI decreased from 45.8 kg/m2 (± 7.7) to 32.3 kg/m2 (± 7.0). Mean percent excess body weight lost was 45.7% (± 17.1) during the first year. Major improvements occurred in arthritis, asthma, depression, diabetes, gastro-esophageal reflux disease, hyperlipidemia, hypertension, joint and back pain, sleep apnea and stress incontinence. Medication usage declined remarkably. Quality of life (QoL) by the SF-36 showed highly significant improvements. Conclusions: At 1 year after LAGB, patients had experienced significant weight loss, resolution of comorbidities, decreases in medication usage, and improvements in QoL.

Diagnostic utility of the history and physical examination for peripheral vascular disease among patients with diabetes mellitus

BACKGROUND We assessed the value of the medical history and physical examination in the diagnosis of peripheral vascular disease in diabetic subjects. METHODS We performed a cross-sectional study in 631 diabetic veteran enrollees of a general internal medicine clinic that compared data obtained from a history and clinical evaluation with the presence of severe peripheral vascular disease defined as an ankle-arm index (AAI) < or = 0.5 derived from Doppler blood pressure measurement. RESULTS We identified 90 limbs with an AAI < or = 0.5. Results presented below apply to the right leg, but do not differ from the left. Diminished or absent foot peripheral pulses (sensitivity 65%, specificity 78%), venous filling time > 20 sec (sensitivity 22%, specificity 93.9%), age > 65 years (sensitivity 83%, specificity 54%), claudication symptoms in < 1 block (sensitivity 50%, specificity 87%), and patient reported history of physician diagnosed peripheral vascular disease (PVD) (sensitivity 80%, specificity 70%) had the largest positive (or smallest negative) likelihood ratios. Capillary refill time > 5 sec or foot characteristics (absent hair, blue/purple color, skin coolness, or atrophy) conveyed little diagnostic information. Individual factors did not change disease probability to a clinically important degree. A stepwise logistic regression model identified four factors significantly (p < 0.05) associated with low AAI: absent or diminished peripheral pulses, patient reported history of PVD, age, and venous filling time. Substitution of < 1 block claudication for PVD history in this model resulted in a small reduction in model accuracy. CONCLUSIONS Many purportedly useful historical and exam findings need not be elicited in diabetic patients suspected of having severe peripheral vascular disease, since most information related to probability of this disorder may be obtained from patient age, self-reported history of physician diagnosed PVD (or < 1 block claudication), peripheral pulse palpation, and venous filling time.

The Health and Functional Status of Veterans With Diabetes

OBJECTIVE To determine the extent of functional impairment among veterans with diabetes and investigate whether such functional impairment is associated with measures of glycemic control, sensory neuropathy, lower extremity macrovascular disease, or other comorbid conditions. RESEARCH DESIGN AND METHODS A 20-item general health survey (SF-20) developed by the Medical Outcomes Study (MOS) Group, was administered to 577 subjects participating in a prospective study of risk factors for diabetic foot ulceration. Measures of glycemic control and neurovascular disease included GHb, sensory lower extremity neuropathy assessed by aesthesiometry, and segmental lower extremity doppler blood pressures. RESULTS Veterans with diabetes have major decreases in all domains of functional status; 87% were in poor health in terms of physical functioning and 86% in terms of health perceptions. Those with advancing age, symptoms of neuropathy and claudication, and a medical history of complications associated with diabetes had significantly more impairment of health status than those without. GHb values did not correlate with functional status measures. Subjects with neuropathy had statistically significant functional impairment. Subjects with vasculopathy had only two significantly low health status measures. CONCLUSIONS In summary, the findings from this survey reveal that veterans with diabetes have low functional status scores. The presence of symptoms and complications accounts for only part of the impairments experienced by this group.

Prospective study of autonomic neuropathy as a predictor of mortality in patients with diabetes

OBJECTIVE The objective of this study is to evaluate whether autonomic neuropathy predicts short term all-cause mortality in an elderly cohort of veteran patients with diabetes. RESEARCH DESIGN AND METHODS All of the diabetic patients receiving primary care at one VA medical center were eligible for participation, between 1990 and 1997. One thousand and fifteen patients were identified, of whom 14% declined to participate, so that a total of 843 diabetic patients were enrolled. Autonomic neuropathy was evaluated by heart rate response to timed deep breathing. One hundred and fifty one patients have died since the onset of the study. RESULTS Mean follow-up was 42.4 months. Subjects who died had greater diabetes duration compared with survivors (13.1 vs. 11.4 years, P=0.04) but were comparable with regards to type of diabetes and mean glycosylated hemoglobin level. The Cox proportional hazards analysis, adjusting for age, smoking status, creatinine, pack-years of cigarettes smoked, diabetes duration, race, history of ischemic heart disease and hypertension showed that those patients with the lowest quintile of heart rate variability had a significantly increased risk of mortality (hazard ratio=1.49, 95% confidence limits 1.01-2.19). CONCLUSIONS This study supports the hypothesis that decreased heart rate variability is an independent risk factor for mortality in diabetic patients followed in a primary care setting.

Responsiveness of the SF-36 among veterans with diabetes mellitus

To examine the responsiveness of the Medical Outcomes Study 36-Item Short Form (SF-36) to the development of diabetes complications over time. We studied a cohort of 331 diabetic veterans participating in a prospective study of risk factors for foot complications. Eight SF-36 scales [general health (GH), physical functioning (PF), social functioning (SF), mental health (MH), physical role (RP), emotional role (RE), bodily pain (BP), and vitality (VT)] and 25 diabetes complications characteristics (DCC) from history and symptom questionnaires and physical exam findings were compared over a mean interval of 3.1 years. The subjects were mostly married, white males with a mean age of 63.5 years, with primarily type 2 diabetes (91%) and a mean diabetes duration of 9.7 years at baseline. There was a statistically significant interval decrease in the GH scale of 6.1 points (effect size [ES] 0.24), PF decreased 9.7 (ES 0.38), SF decreased 5.8 (ES 0.19), PR decreased 14.7 (ES 0.38), BP decreased 4. 0 (ES0.14), VT decreased 4.5 (ES 0.16), total DCC increased by 1.8 (ES 0.53), and hemoglobin A(1c) declined 1.3% (ES 0.48). An increase of >1 DCC was associated with an average loss of 7.2 to 11.8 points on six SF-36 scales (GH, PF, SF, RP, BP, VT). The development of any renal complication was related to decrements in five SF-36 scales (GH, PF, SF, RP, VT) while the appearance of any neuropathy complication was associated with a decline in four SF-36 scales (GH, PF, PR, VT). These results imply that six of the SF-36 scales are responsive to the development of diabetes complications over time among elderly veterans, supporting their use in longitudinal research. Renal and neuropathy complications have the greatest effects on the SF-36.