Persons with diabetes have a higher incidence of fractures compared with persons without diabetes. However, there is little published information concerning the deleterious effect of late-stage diabetes on fracture healing. There are no studies using animal models that evaluate the effect of advanced diabetes on fracture healing. The purpose of our study was to evaluate cytokine expression, specifically macrophage inflammatory protein 1 (MIP-1) and vascular endothelial growth factor, in fracture healing in a type 2 diabetes rat model.
We evaluated biomarker expression after femur fracture using a rat model. The two groups consisted of 24 Zucker diabetic rats (study group) and 12 Zucker lean rats (control group). An independent reviewer was used to assess delayed union. We evaluated serum samples 2, 4, 7, and 14 days after surgery for MIP-1, vascular endothelial growth factor, leptin, and other cytokine levels.
At 3 weeks, Kaplan-Meier estimates showed that 45.8% of femur fractures in Zucker diabetic rats had healed, whereas 81.8% of those in Zucker lean rats had healed (P = .02). A logistic regression model to predict fast healing that included the three cytokines and diabetes status showed that the only factor achieving significance was MIP-1α. Vascular endothelial growth factor was the only biomarker to show significance compared with delayed healing.
These results confirm significant differences in biomarker expression between diabetic and nondiabetic rats during bone healing. The key factors for bone healing may appear early in the healing process, whereas differences in diabetes versus nondiabetes are seen later in the healing process. Increased levels of MIP-1α were associated with the likelihood of delayed healing.
Background: The aim of this study was to evaluate the incidence and recovery of acute kidney injury (AKI) in patients admitted to the hospital with and without diabetes mellitus (DM) with foot infections.
Methods: We retrospectively reviewed 294 patients with DM and 88 without DM admitted to the hospital with foot infections. The Kidney Disease: Improving Global Outcomes guidelines were used to define AKI. Recovery was divided into three categories: full, partial, and no recovery within 90 days of the index AKI.
Results: The AKI incidence was 3.0 times higher in patients with DM (DM 48.5% versus no DM 23.9%; 95% confidence interval [CI], 1.74–5.19; P < .01). Acute kidney injury incidence was similar at each stage in people with and without DM (stage 1, DM 58.1% versus no DM 47.6%; stage 2, DM 23.3% versus no DM 33.3%, and stage 3, DM 18.6% versus no DM 19.1%). Twenty-nine patients with diabetes had a second AKI event and four had a third event. In patients without DM, one patient had a second AKI. Cumulative AKI incidence was 4.7 times higher in people with DM (DM 60.9% versus no DM 25.0%; 95% CI, 2.72–8.03; P < .01). Patients with diabetes progressed to chronic kidney disease or in chronic kidney disease stage 39.4% of the time. Patients without diabetes progressed 16.7% of the time, but this trend was not significant (P = .07). Complete recovery was 3.8 times more likely in patients without diabetes (95% CI, 1.26–11.16; P = .02).
Conclusions: Acute kidney injury incidence is higher in patients with diabetes, and complete recovery after an AKI is less likely compared to patients without diabetes.
Background: This study was designed to compare the vitamin D levels in a cohort of nondiabetic patients to populations of diabetic patients with and without Charcot neuroarthropathy.
Methods: A total of 41 participants (22 male, 19 female) with a mean ± SD age of 59 ± 9.43 years had serum 25-hydroxyvitamin D levels tested. Fifteen participants composed the nondiabetic group; 13, the group with diabetes but without Charcot neuroarthropathy; and 13, the group with both diabetes and Charcot neuroarthropathy.
Results: The results of the study showed that the vitamin D levels in both diabetic populations were significantly lower (P < .05) than the nondiabetic population. There was no statistical difference between the group with diabetes but without Charcot foot disease and the group with both diabetes and Charcot neuroarthropathy.
Conclusions: Based on the results of this study, given the importance of vitamin D in bone metabolism and the osseous consequences associated with diabetes, as well as other systems affected by low levels of vitamin D in the diabetic patient, it appears that vitamin D levels should be monitored in diabetic patients. (J Am Podiatr Med Assoc 99(1): 35–41, 2009)
Charcot's arthropathy (CA) is a destructive rare complication of diabetes, and its diagnosis remains challenging for foot specialists and surgeons. We aimed to assess the clinical presentation and characteristics of CA and the frequencies of its various types.
This cross-sectional study was conducted from January 1, 2007, to December 31, 2016, and included 149 adults with diabetes diagnosed as having CA. Cases of CA were classified based on the Brodsky anatomical classification into five types according to location and involved joints.
The mean ± SD age of the studied cohort was 56.7 ± 11 years, with a mean ± SD diabetes duration of 21.2 ± 7.0 years. The CA cohort had poorly controlled diabetes and a high rate of neuropathy and retinopathy. The most frequent type of CA was type 4, with multiple regions involved at a rate of 56.4%, followed by type 1, with midfoot involvement at 34.5%. A total of 47.7% of the patients had bilateral CA. Complications affected 220 limbs, of which 67.7% had foot ulceration. With respect to foot deformity, hammertoe affected all of the patients; hallux valgus, 59.5%; and flatfoot, 21.8%.
There is a high rate of bilateral CA, mainly type 4, which could be attributed to cultural habits in Saudi Arabia, including footwear. This finding warrants increasing awareness of the importance of maintaining proper footwear to avoid such complications. Implementation of preventive measures for CA is urgently needed.
The Diabetic Foot 2001
A Summary of the Proceedings of the American Diabetes Association’s 61st Scientific Symposium
This review discusses some of the significant studies and events from the 61st American Diabetes Association’s Scientific Symposium. Many of the issues raised at the meeting will form building blocks for future research into offloading, footwear, wound classification, wound healing, tissue engineering, and psychological aspects of therapy and prevention. (J Am Podiatr Med Assoc 92(1): 2-6, 2002)
Objective: To investigate the predictive value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in persons with and without diabetes with osteomyelitis (OM).
Methods: We evaluated 455 patients in a retrospective cohort study of patients admitted to the hospital with diabetic foot OM (n = 177), diabetic foot soft-tissue infections (STIs) (n = 176), nondiabetic OM (n = 51), and nondiabetic STIs (n = 51). Infection diagnosis was determined through bone culture, histopathologic examination for OM, and/or imaging (magnetic resonance imaging/single-photon emission computed tomography) for STI. The optimal cutoff values of ESR and CRP in predicting OM were determined by receiver operating characteristic curve analysis. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were determined through contingency tables.
Results: In persons without diabetes with STI or OM, the mean ESR and CRP differences were 10.0 mm/h and 2.6 mg/dL, respectively. In contrast, persons with diabetes had higher levels of each: 24.8 mm/h and 6.8 mg/dL, respectively. As a result, ESR and CRP predicted OM better in patients with diabetes. However, when patients were stratified by neuropathy status, ESR remained predictive of OM in diabetic patients with neuropathy (75% sensitivity, 58% specificity) but not in diabetic patients without neuropathy (50% sensitivity, 44% specificity). Also, CRP remained predictive irrespective of neuropathy status. A similar trend was observed in patients without diabetes.
Conclusions: Previous studies have reported that ESR and CRP are predictive of OM. However, this study suggests that neuropathy influences the predictive value of inflammatory biomarkers. The underlying mechanisms require further study.
The Amputation Prevention Initiative is a project conducted jointly by the Massachusetts Public Health Association and the Massachusetts Podiatric Medical Society that seeks to study methods to reduce nontraumatic lower-extremity amputations from diabetes.
To determine the rate of diabetes-related lower-extremity amputations in Massachusetts and identify the groups most at risk, hospital billing and discharge data were analyzed. To examine the components of the diabetic foot examination routinely performed by general practitioners, surveys were conducted in conjunction with physician meetings in Massachusetts (n = 149) and in six other states (n = 490).
The average age-adjusted number of diabetes-related lower-extremity amputations in 2004 was 30.8 per 100,000 and 5.3 per 1,000 diabetic patients in MA, with high-risk groups being identified as men and black individuals. Among the general practitioners surveyed in Massachusetts, only 2.01% reported routinely conducting all four key components of the diabetic foot examination, with 28.86% reporting not performing any components.
These findings suggest that many general practitioners may be failing to perform the major components of the diabetic foot examination believed to prevent foot ulcers and lower-extremity amputations.
This prospective study was performed to compare calcaneal and lumbar bone mineral density (BMD) in individuals with and without diabetes mellitus. We compared bone density with the time from onset of Charcot’s neuroarthropathy (CN) in patients with unilateral, nonoperative, reconstructive-stage CN. The final purpose was to investigate the role that sex, age, and serum vitamin D level may have in osseous recovery.
Thirty-three individuals were divided into three groups: controls and patients with diabetes mellitus with and without CN. Peripheral instantaneous x-ray imaging and dual-energy x-ray absorptiometry were performed.
The calcaneal BMD of patients with diabetes mellitus and CN was lower than that of the control group (P < .01) but was not significantly lower than that of patients with diabetes mellitus alone. There was no statistically significant difference in lumbar T-scores between groups. Women demonstrated lower BMD than did men (P = .02), but patients 60 years and older did not demonstrate significantly lower BMD than did patients younger than 60 years (P = .135). A negative linear relationship was demonstrated between time and BMD in patients with CN.
The results of this study suggest that lumbar BMD does not reflect peripheral BMD in patients with diabetes mellitus and reconstructive-stage CN. This study has clinical implications when reconstructive osseous surgery is planned in patients with CN. (J Am Podiatr Med Assoc 102(3): 213–222, 2012)
Background: The diabetic foot is one of the main complications of diabetes mellitus, with a high risk of minor or major amputation. The preclinical foot lesions of patients without foot complaints were compared with healthy controls and analyzed.
Methods: This study was conducted with 89 diabetic patients from an endocrinology clinic and 35 nondiabetic control patients. The patients were asked about the presence, types, and durations of pedal complaints; acquired and congenital foot deformities; and atrophy. Patient gaits were inspected for any swelling; skin and nail changes were also recorded. Ranges of articular motion, deformities, crepitations, and any painful perceptions were noted.
Results: The differences between groups were significant for sensorial defects, joint changes of the foot, nail abnormalities, and neuropathic changes.
Conclusions: Every patient with an established diagnosis of diabetes can be considered a potential sufferer of diabetic foot for whom medical therapy and foot protection programs are indicated. (J Am Podiatr Med Assoc 99(2): 114–120, 2009)
Microvascular dysfunction is an important component of the pathologic processes that occur in diabetic foot disease. The endothelial abnormalities observed in patients with diabetes mellitus are poorly understood, and evidence suggests that endothelial dysfunction could be involved in the pathogenesis of diabetic macroangiopathy and microangiopathy. With the advent of insulin replacement in the early 1900s and increased efforts toward metabolic control of diabetes, long-term complications of this disease have become apparent. These late-term complications are primarily disorders of the vascular system. This article reviews the process of microvascular dysfunction and how it may relate to the pathogenesis of diabetic foot problems. (J Am Podiatr Med Assoc 96(3): 245–252, 2006)