Effects of a DASH-like diet containing lean beef on vascular health.

A DASH (dietary approaches to stop hypertension) dietary pattern rich in fruits and vegetables and low-fat dairy products with increased dietary protein provided primarily from plant protein sources decreases blood pressure. No studies, however, have evaluated the effects of a DASH-like diet with increased dietary protein from lean beef on blood pressure and vascular health. The aim of this study was to study the effect of DASH-like diets that provided different amounts of protein from lean beef (DASH 28 g beef per day; beef in an optimal lean diet (BOLD) 113 g beef per day; beef in an optimal lean diet plus additional protein (BOLD+) 153 g beef per day) on blood pressure, endothelial function and vascular reactivity versus a healthy American diet (HAD). Using a randomized, crossover study design, 36 normotensive participants (systolic blood pressure (SBP), 116 ± 3.6 mm Hg) were fed four isocaloric diets,: HAD (33% total fat, 12% saturated fatty acids (SFA), 17% protein (PRO), 20 g beef per day), DASH (27% total fat, 6% SFA, 18% PRO, 28 g beef per day), BOLD (28% total fat, 6% SFA, 19% PRO, 113 g beef per day) and BOLD+ (28% total fat, 6% SFA, 27% PRO, 153 g beef per day), for 5 weeks. SBP decreased (P<0.05) in subjects on the BOLD+ diet (111.4 ± 1.9 mm Hg) versus HAD (115.7 ± 1.9). There were no significant effects of the DASH and BOLD diets on SBP. Augmentation index (AI) was significantly reduced in participants on the BOLD diet (-4.1%). There were no significant effects of the dietary treatments on diastolic blood pressure or endothelial function (as measured by peripheral arterial tonometry). A moderate protein DASH-like diet including lean beef decreased SBP in normotensive individuals. The inclusion of lean beef in a heart healthy diet also reduced peripheral vascular constriction.

A high-legume low-glycemic index diet reduces fasting plasma leptin in middle-aged insulin-resistant and -sensitive men.

Fasting leptin and ghrelin levels were measured in 36 insulin-sensitive (IS) and 28 insulin-resistant (IR) men who consumed a legume-enriched low-glycemic index (LG) diet or healthy American (HA) diet in a randomly ordered cross-over feeding study consisting of two 4-week periods. Weight remained stable over the entire study. Fasting plasma leptin was significantly reduced from pre-study levels by both the LG (18.8%, P < 0.001) and HA (16.1%, P < 0.001) diets, whereas fasting ghrelin did not change. By subgroup analysis according to prestudy insulin status, leptin was reduced in IR subjects after both the LG (17.1%, P < 0.01) and the HA (33.3%, P < 0.001) diets, whereas IS subjects responded only after the LG diet (23.1%, P < 0.01). Thus, a legume-rich LG index diet may be a beneficial strategy for reducing circulating leptin concentrations, even under conditions of weight maintenance.

Depression predicts first but not recurrent diabetic foot ulcers.

AIMS/HYPOTHESIS: This study examined the relationship between symptoms of depression and the development of diabetic foot ulcers. METHODS: Participants were 333 patients (71% male; mean age 62 years; 73% with type 2 diabetes) with diabetic peripheral neuropathy (DPN), but without peripheral vascular disease (PVD). Severity of DPN and the presence of PVD were assessed by clinical examination. Depression, other diabetes complications and foot self-care were assessed by self-report. Cox regression tested whether depression was an independent predictor of foot ulceration over 18 months, whether this relationship was moderated by foot ulcer history, and whether foot self-care mediated this relationship. RESULTS: During follow-up, 63 patients developed a foot ulcer. Those with prior foot ulcers had more than four-fold greater risk of subsequent foot ulceration compared with those without a history of foot ulcer. A significant interaction effect showed that depression was significantly related to the development of first but not recurrent foot ulcers. This relationship was independent of biological risk factors. In the final model, each standard deviation increase in depression symptoms was significantly associated with increased risk of developing first foot ulcers (HR 1.68, 95% CI 1.20-2.35), while foot self-care was associated with lower risk (HR 0.61, 95% CI 0.40-0.94). Foot self-care did not mediate the relationship between depression and foot ulceration. CONCLUSIONS/INTERPRETATION: These data suggest that depression is associated with increased risk of first foot ulcers in DPN patients and that this relationship is independent of biological risk factors and foot self-care. Interventions that target depression and foot self-care before the development of foot ulcers may maximise the likelihood of successful prevention of foot ulceration.

Plantar pressures in diabetic patients with foot ulcers which have remained healed.

AIMS: The recurrence of foot ulcers is a significant problem in people with diabetic neuropathy. The purpose of this study was to measure in-shoe plantar pressures and other characteristics in a group of neuropathic patients with diabetes who had prior foot ulcers which had remained healed. METHODS: This was an epidemiological cohort study of patients from diabetes clinics of two Swedish hospitals. From a database of 2625 eligible patients, 190 surviving patients with prior plantar ulcers of the forefoot (hallux or metatarsal heads) caused by repetitive stress were identified and 49 patients agreed to participate. Barefoot and in-shoe plantar pressures were measured during walking. Data on foot deformity, activity profiles and self-reported behaviour were also collected. RESULTS: Mean barefoot plantar peak pressure at the prior ulcer site (556 kPa) was lower than in other published series, although the range was large (107-1192 kPa). Mean in-shoe peak pressure at this location averaged 207 kPa when measured with an insole sensor. Barefoot peak pressure only predicted approximately 35% of the variance of in-shoe peak pressure, indicating variation in the efficacy of the individual footwear prescriptions (primarily extra-depth shoes with custom insoles). CONCLUSIONS: We propose that the mean value for in-shoe pressures reported in these patients be used as a target in footwear prescription for patients with prior ulcers. Although plantar pressure is only one factor in a multifaceted strategy to prevent ulcer recurrence, the quantitative focus on pressure reduction in footwear is likely to have beneficial effects.

Predictors of depressive symptoms in persons with diabetic peripheral neuropathy: a longitudinal study.

AIMS/HYPOTHESIS: The aim of the study was to determine whether diabetic peripheral neuropathy (DPN) is a risk factor for depressive symptoms and examine the potential mechanisms for this relationship. METHODS: This longitudinal study (9 and 18 month follow-up) of 338 DPN patients (mean age 61 years; 71% male; 73% type 2 diabetes) examined the temporal relationships between DPN severity (mean +/- SD; neuropathy disability score [NDS], 7.4 +/- 2.2; mean vibration perception threshold, 41.5 +/- 9.5 V), DPN somatic experiences (symptoms and foot ulceration), DPN psychosocial consequences (restrictions in activities of daily living [ADL] and social self-perception) and the Hospital Anxiety and Depression subscale measuring depressive symptoms (HADS-D; mean 4.9 +/- 3.7). RESULTS: Controlling for baseline HADS-D and demographic/disease variables, NDS at baseline significantly predicted increased HADS-D over 18 months. This association was mediated by baseline unsteadiness, which was significantly associated with increased HADS-D. Baseline ADL restrictions significantly predicted increased HADS-D and partly mediated the association between baseline unsteadiness and change in HADS-D. Increased pain, unsteadiness and ADL restrictions from baseline to 9 months each significantly predicted increased HADS-D over 18 months. Change in social self-perception from baseline to 9 months significantly predicted increased HADS-D and partly mediated the relationships of change in unsteadiness and ADL restrictions with change in HADS-D. CONCLUSIONS/INTERPRETATION: These results confirm that neuropathy is a risk factor for depressive symptoms because it generates pain and unsteadiness. Unsteadiness is the symptom with the strongest association with depression, and is linked to depressive symptoms by perceptions of diminished self-worth as a result of inability to perform social roles.

Vibration perception threshold testing in patients with diabetic neuropathy: ceiling effects and reliability.

AIMS: To test the reliability of a new vibrometer (Maxivibrometer) which was constructed so that vibration perception threshold (VPT) could be determined without the disadvantage of the off-scale measurements frequently experienced with the Biothesiometer. METHODS: The two devices were compared and tested on a group of diabetic neuropathic subjects and a group of healthy, matched control subjects. VPT was tested on the plantar surface of the feet. RESULTS: The Maxivibrometer gave an actual measurement in all cases even if subjects were severely neuropathic. The replication-to-replication and day-to-day intraclass correlation coefficients for the Maxivibrometer VPT were, except in one case, above 0.94, indicating excellent reliability. The Biothesiometer VPT could also be measured with excellent reliability but only within a limited range of mild to moderate neuropathy, so it appears to be an appropriate screening tool. The replication-to-replication intraclass correlation coefficient was 0.93. CONCLUSIONS: Because VPT could be measured over a wide range with the Maxivibrometer, it was demonstrated that loss of sensation in diabetic neuropathy can progress far beyond the maximum VPT value of the Biothesiometer. The wide measurement range and the excellent reliability make the Maxivibrometer a valuable research tool to quantify loss of sensation, particularly in the presence of severe neuropathy and to record changes over time. Diabet. Med. 18, 469-475 (2001)

Design criteria for rigid rocker shoes.

In this study nine different rigid rocker shoe designs were tested in 17 symptom-free male subjects and compared with the control condition of a flexible, non-rockered extra-depth shoe with the same flat insole. Effects of both rocker height and axis location were explored. Peak pressure was reduced at most forefoot locations by rocker shoes, but increased in the midfoot and heel. Axis location was found to have an important effect, particularly on hallux pressures. On average the best axis location for reducing metatarsal head (MTH) pressure was in the region of 55-60% of shoe length, while for the toes it was 65%. There was a mean trend towards optimal reduction of pressure in one of the rocker shoe conditions at each anatomical location, but the axis position for this optimal placement was variable across subjects and anatomical locations. While most configurations of the rocker shoes were superior to the control shoe, no single configuration was optimal for all subjects at all sites or even for all subjects at the same site. Therefore, some form of plantar pressure measurement in conjunction with gait training to ensure correct use of the rocker shoes would appear to be essential if the pressure reducing effect of the rigid rocker bottom shoe is to be optimized.

New developments in the biomechanics of the diabetic foot.

Biomechanical issues are now widely recognized as being important in the treatment of diabetic foot disease. The purpose of the present review is to identify advances that have occurred since the previous International Conference on the Diabetic Foot in 1995 in the understanding of foot biomechanics in relation to diabetes. Attention continues to be focused on the identification of a threshold plantar pressure that leads to tissue damage. Recent studies have suggested that peak barefoot pressure may be only 65% specific for the development of ulceration. The association between foot deformity and plantar pressure has been the subject of several quantitative studies, but new questions have been raised about the etiology of claw toes. The measurement of shear stress continues to be an elusive goal although several small studies have presented possibly feasible technical approaches. The importance of callus as a precursor to ulceration has been confirmed experimentally and quantitative measures of motor neuropathy have been presented. Although a number of new devices have been introduced as alternatives to the Total Contact Cast, few clinical studies of their efficacy are available yet. New information on the properties of insole materials has been published including data on changes with repeated cycling. Complications of prophylactic surgery have been shown to include a high rate of Charcot fractures. Two new series describing the fixation of such fractures have also been reported. Biomechanical issues have also been addressed in two sets of guidelines for treatment that have recently been published. These many studies confirm the central role of mechanical stress and its relief in the treatment of neuropathic foot problems in diabetes.

Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle.

Physiological stress associated with muscle damage results in systemic insulin resistance. However, the mechanisms responsible for the insulin resistance are not known; therefore, the present study was conducted to elucidate the molecular mechanisms associated with insulin resistance after muscle damage. Muscle biopsies were obtained before (base) and at 1 h during a hyperinsulinemic-euglycemic clamp (40 mU x kg(-1) x min(-1)) in eight young (age 24+/-1 yr) healthy sedentary (maximal O(2) consumption, 49.7+/-2.4 ml x kg(-1) x min(-1)) males before and 24 h after eccentric exercise (ECC)-induced muscle damage. To determine the role of cytokines in ECC-induced insulin resistance, venous blood samples were obtained before (control) and 24 h after ECC to evaluate ex vivo endotoxin-induced mononuclear cell secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta. Glucose disposal was 19% lower after ECC (P<0.05). Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation was 45% lower after ECC (P<0.05). Insulin-stimulated phosphatidylinositol (PI) 3-kinase, Akt (protein kinase B) serine phosphorylation, and Akt activity were reduced 34, 65, and 20%, respectively, after ECC (P < 0.05). TNF-alpha, but not IL-6 or IL-1beta production, increased 2.4-fold 24 h after ECC (P<0.05). TNF-alpha production was positively correlated with reduced insulin action on PI 3-kinase (r = 0.77, P = 0.04). In summary, the physiological stress associated with muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase, presumably leading to decreased insulin-mediated glucose uptake. Although more research is needed on the potential role for TNF-alpha inhibition of insulin action, elevated TNF-alpha production after muscle damage may impair insulin signal transduction.

Fluid snacks to help persons with type 1 diabetes avoid late onset postexercise hypoglycemia.

PURPOSE: The present study assessed whether whole milk, skim milk, or two commercially available sports drinks are effective in preventing late onset postexercise hypoglycemia (LOPEH) in persons with type 1 diabetes mellitus. METHODS: Subjects ingested water, whole milk, skim milk, sport drink A (carbohydrate and electrolytes), or sport drink B (carbohydrate, fat, and protein) before, during, and after 1 h of bicycle exercise at 60% VO2max in the late afternoon. Drinks were isocaloric (470 +/- 150 kcal) and the number of calories consumed was based on individual energy expenditure. No adjustment in insulinization was allowed in anticipation of exercise. RESULTS: During water trials all subjects became hypoglycemic. Most drinks lead to a moderate hyperglycemia (range of mean values = 200-280 mg x dL(-1)) during the period between the end of exercise and dinner, but this was not the case for whole milk (range 80-120 mg x dL(-1)). Glycemia peaked about 1.5 h after dinner and declined over the next 90 min. Persistent hyperglycemia (range of means = 200-310 mg x dL(-1)) from after exercise to about 4 h postexercise was observed with sports drink B. A decline in glycemia in the evening was greatest during the skim milk trial and required subjects to ingest more carbohydrate as a late evening snack. The least decline during this period occurred during the whole milk trial. Subjects experienced pre-bed and early morning (0300 h) hypoglycemia in 7 of the 28 trials. CONCLUSIONS: These data show that whole milk and sports drinks that are designed for both quick (sport drink A) and long lasting (sport drink B) nutrient replenishment can be used by persons with type 1 diabetes in an effort to avoid LOPEH.

Neuropathic gait shows only trends towards increased variability of sagittal plane kinematics during treadmill locomotion.

Patients with diabetes mellitus (DM) and peripheral neuropathy (PN) are at greater risk of falling and of suffering injuries during falls. It has been hypothesized that PN leads to changes in gait variability that may account for this increased risk. The purpose of this investigation was to analyze the variability of the sagittal plane kinematics of diabetic neuropathic (NP), diabetic non-neuropathic (NNP) and age- and weight-matched control subjects (Control) during motorized treadmill walking at constant speed. While there were distinct trends towards increased variability within the three diagnostic groups (NP > NNP > Control) for several measures of gait variability, most of these trends were not statistically significant. We hypothesize that motorized treadmill walking may be inherently less variable than overground walking and that statistical measures of variability may not be sufficient to fully characterize stride-to-stride variability in human locomotion.

Elevated plantar pressure and ulceration in diabetic patients after panmetatarsal head resection: two case reports.

Panmetatarsal head resection (variously called forefoot arthroplasty, forefoot resection arthroplasty, the Hoffman procedure, and the Fowler procedure) was developed for the relief of pain and deformity in rheumatoid arthritis. Although there are successful retrospective series reported in the literature, such an approach is not supported by carefully designed controlled trials. This procedure has also been advocated by some for the relief of plantar pressure in diabetic patients who are at risk for plantar ulceration. The efficacy of the procedure in this context is not supported by existing pressure measurements on rheumatoid arthritis patients in the literature, which has tended to show that although pain relief is obtained, the procedure results in elevation of forefoot pressure. Case reports are described of two patients (three feet) with sensory neuropathy who presented to our clinic 1 to 2 years after panmetatarsal head resections had been performed. Peak plantar pressures in these feet during first step gait were above the 99th percentile and outside the measuring range of the device used (EMED SF platform; NOVEL Electronics Inc., St. Paul, MN). Both patients had also experienced plantar ulcers subsequent to the surgery. Combining the information on patients with rheumatoid arthritis (RA) with that from our two case studies, we conclude that panmetatarsal head resection does not necessarily eliminate focal regions of elevated plantar pressure.

The non-healing diabetic foot wound: fact or fiction?

Wounds on the feet of diabetic patients are often labeled as "non-healing." This article discusses the basis for and the dangers of such a classification. The evidence suggests that if the foot has an adequate vascular supply and no significant infection, a plantar wound that does not heal is the result of poor treatment and/or poor compliance. Wounds that do not heal despite optimal treatment and compliance are extremely rare and need to be referred to the appropriate specialist for care.

The role of muscle spindles in ankle movement perception in human subjects with diabetic neuropathy.

The objective of this study was to develop a quantitative method to assess muscle spindle function. Three groups of subjects were studied: ten young and healthy subjects, 15 older subjects with diabetic neuropathy, and 15 age-matched controls. All subjects performed an ankle-movement matching task with and without muscle vibration. Input from the plantar cutaneous mechanoreceptors was minimized by using a foot-clamping device. The younger subjects tracked the movement very well, but vibration had a significant effect on their performance (P < 0.001). Similar results were seen in the older control subjects, but they were less successful in tracking movement and slightly less affected by vibration. The neuropathic subjects had the most difficulty tracking, and vibration had only a small but still significant effect on their performance. The interaction between the group and the vibration effect was highly significant (P < 0.001), indicating that the performance of the control subjects changed to a greater degree in the presence of vibration than the performance of the subjects with diabetic neuropathy. Muscle spindles are the primary receptors that are involved in the change in tracking performance when vibration is added during an ankle-movement matching task, and we therefore conclude that the procedure described provides a quantitative evaluation of muscle spindle function. The results demonstrate that diabetic neuropathy degrades muscle sensory function, which may contribute to the impaired balance and unsteadiness of gait that has been observed in diabetic neuropathy.

Sibutramine reduces food intake in non-dieting women with obesity.

Sibutramine (SIB), an inhibitor of serotonin and noradrenaline reuptake, has been shown in clinical trials to be associated with a dose-related decrease in bodyweight. This double-blind, placebo-controlled, Latin square crossover study examined whether the effect on bodyweight could be due in part to a reduction in daily food intake. Twelve non-dieting, women with obesity (body mass index of 30.5 to 41.9) received three treatments (0 [matching placebo], 10, or 30 mg SIB/day) for 14 days, with 14-day washout periods in between. On days 7 and 14, participants came to the laboratory to eat breakfast, lunch, and dinner so that daily energy and macronutrient intakes and ratings of hunger and satiety could be measured. Significant reductions occurred in food intake (both grams and energy) over the 14-day study period. On day 7, SIB 30 reduced intake significantly by 1762 kJ (23% reduction from placebo), and on day 14, both SIB 10 and SIB 30 significantly reduced intake compared with placebo (SIB 10, 19% reduction [1490 kJ]; SIB 30, 26% reduction [2079 kJ]). On day 7, the percentage of energy consumed from carbohydrate increased significantly with the 30-mg dose (56.7%) compared with that of placebo (51.4%), with a reciprocal decrease in energy from fat (27.8% to 24%). The results show that SIB reduced energy intake in women with obesity who were not attempting to lose weight.

The effect of insoles in therapeutic footwear--a finite element approach.

Current practice in the prevention of recurrence of neuropathic foot ulcers is to prescribe accommodative in-shoe orthoses or insoles which reduce plantar pressure levels at locations of bony prominences, particularly under the metatarsal heads. To date, design of these orthoses has largely been a trial and error process. There is little quantitative information available regarding the effects of thickness and the influence of soft tissue characteristics on the cushioning effect of such interventions. The current paper investigated alterations in pressure under the second metatarsal head as a function of insole thickness and tissue thickness. Both experimental and quasi-static plane strain finite element approaches were employed. The orthoses chosen reduced plantar pressure by a maximum of approximately 30% and were more effective (on a percentage basis) in the setting of reduced sub-metatarsal tissue thickness. Peak normal stresses predicted by the FE models were, on average, within 5.9% of experimentally measured values for the normal tissue case and 8.1% for the reduced tissue case. The techniques presented represent a promising approach to understanding plantar cushioning and the principles involved in the design of therapeutic footwear for insensate feet.

The total contact cast: a method for treating neuropathic diabetic ulcers.

Plantar ulcers that do not heal in patients with diabetes and peripheral sensory neuropathy have been shown to be precursors of lower extremity amputation. The total contact cast is considered by many authorities to be the most effective technique for healing of wounds in the neuropathic extremity, yet it still is not widely used in clinical practice. Use of the total contact cast allows mobilization and results in diminished edema and decreased pressure over the ulcerated area. Complete healing usually occurs in eight weeks or less. Total contact casting with careful follow-up should be considered as a useful modality for healing plantar ulcers in diabetic patients with neuropathy of the extremities.

The mechanism of plantar unloading in total contact casts: implications for design and clinical use.

Although the total contact cast (TCC) has been shown to be an extremely effective treatment for the healing of plantar ulcers in diabetic patients, little is known about the biomechanics of its action. In this study, plantar pressure and ground reaction force measurements were obtained from over 750 foot contacts as five subjects with known elevated plantar forefoot pressures walked barefoot, in a padded cast shoe, and a TCC. Peak plantar pressures in the forefoot were markedly reduced in the cast compared with both barefoot and shoe walking (reductions of 75% and 86% respectively, P < 0.05). Peak plantar pressures in the heel were not, however, significantly different between the shoe and the TCC, and the longer duration of heel loading resulted in an impulse that was more than twice as great in the cast compared with the shoe (P < 0.05). An analysis of load distribution indicated that the mechanisms by which the TCC achieves forefoot unloading are (1) transfer of approximately 30% of the load from the leg directly to the cast wall, (2) greater proportionate load sharing by the heel, and (3) removal of a load-bearing surface from the metatarsal heads because of the "cavity" created by the soft foam covering the forefoot. These results point out some of the "essential design features" of the TCC (which are different from what had been previously supposed), support the use of the TCC for healing plantar ulcers in the forefoot, but raise questions about its utility in the healing of plantar ulcers on the heel.