Atherogenic markers and 1-year amputation risk in adults with diabetic foot in a tertiary level hospital: A retrospective cohort study.

AIM: To determine the association between atherogenic markers, such as total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL-C), triglycerides/HDL-C ratio (TG/HDL-C), and triglycerides-glucose index (TyG), and the risk of 1-year amputation in adults with diabetic foot in a tertiary level hospital. METHODS: Retrospective cohort study conducted in 162 adult patients with diabetic foot. The outcome was amputation, defined as "primary amputation in patients' clinical history after their first hospitalization due to foot ulcer.". The cutoff point was determined using Youden's J statistic. The relative risk (RR) was presented as an association measure. RESULTS: A TyG index of >9.4 [RR: 1.64 (1.10-2.45)] was associated with a high risk of amputation after 1-year in adults with diabetic foot. However, while a TC/HDL ratio of >4.69 [RR: 1.38 (0.94-2.03)] and a TG/HDL-C ratio > 3.57 [RR: 1.35 (0.89-2.06)] did not show associations with risk of amputation after 1-year. CONCLUSIONS: Only a TyG index of >9.4 was associated with an increased risk of 1-year amputation in adults with diabetic foot. Future studies with larger samples and a longitudinal design may provide more robust evidence and a better understanding of clinical implications.

Analysis of Circulating miRNA Expression Profiles in Type 2 Diabetes Patients with Diabetic Foot Complications.

Type 2 diabetes mellitus (T2DM) is associated with various complications, including diabetic foot, which can lead to significant morbidity and mortality. Non-healing foot ulcers in diabetic patients are a major risk factor for infections and amputations. Despite conventional treatments, which have limited efficacy, there is a need for more effective therapies. MicroRNAs (miRs) are small non-coding RNAs that play a role in gene expression and have been implicated in diabetic wound healing. miR expression was analyzed through RT-qPCR in 41 diabetic foot Mexican patients and 50 controls. Diabetic foot patients showed significant increases in plasma levels of miR-17-5p (p = 0.001), miR-191-5p (p = 0.001), let-7e-5p (p = 0.001), and miR-33a-5p (p = 0.005) when compared to controls. Elevated levels of miR-17, miR-191, and miR-121 correlated with higher glucose levels in patients with diabetic foot ulcers (r = 0.30, p = 0.004; r = 0.25, p = 0.01; and r = 0.21, p = 0.05, respectively). Levels of miR-17 showed the highest diagnostic potential (AUC 0.903, p = 0.0001). These findings underscore the possible role of these miRs in developing diabetes complications. Our study suggests that high miR-17, miR-191, and miR-121 expression is strongly associated with higher glucose levels and the development of diabetic foot ulcers.

Evaluación de la seguridad, la validez diagnóstica y la efectividad clínica de la medición transcutánea de la presión parcial de oxígeno en el manejo del pie diabético / Evaluation of the security, validity diagnosis and the clinical effectiveness of transcutaneous measurement of the partial pressure of oxygen in handling diabetic foot

ANTECEDENTES/INTRODUCCIÓN La causa más común de complicaciones y hospitalizaciones entre los pacientes con diabetes mellitus (DM) es el pie diabético, que se define como un síndrome que causa ulceración, infección o gangrena del pie asociada a neuropatía diabética y a diferentes grados de enfermedad arterial periférica (EAP). El 25% de los pacientes con DM se encuentra en riesgo de desarrollar una úlcera en el pie, pudiendo implicar la amputación del miembro inferior y una pérdida de la calidad de vida de los pacientes, así como unos costes sanitarios elevados. La EAP se observa en el 50% de los casos con DM y se asocia con aparición de úlceras, amputación del miembro inferior, complicaciones cardiovasculares y aumento del riesgo de muerte. Por lo tanto, la identificación y evaluación de la EAP tiene un papel importante en el manejo de pacientes con DM y pie diabético. Teniendo en cuenta las necesidades en el manejo del pie diabético, son necesarias tecnologías que permitan: a) identificar la EAP en pacientes con DM, b) pronosticar la evolución del pie diabético y c) seleccionar y monitorizar el tratamiento vascular del pie diabético. Actualmente, se dispone de diferentes pruebas no invasivas que se utilizan en el diagnóstico y seguimiento de la EAP, así como en la clasificación del riesgo de la úlcera. Una de las más utilizadas es el índice tobillo-brazo (ITB). Sin embargo, se ha sugerido que este método presentaría algunas limitaciones, especialmente en pacientes que presentan calcificación de las arterias. Por este motivo, se ha propuesto el uso de la medición transcutánea de la presión parcial de oxígeno (TcPO2 ). Los dispositivos de TcPO2 son tecnologías que estiman la presión parcial de oxígeno en la superficie de la piel mediante un electrodo no invasivo e informan sobre el aporte de oxígeno proveniente de la circulación microvascular subyacente. El objetivo general del presente informe es evaluar el uso de la medición de TcPO2 en el manejo del pie diabético y comparar su seguridad, validez diagnóstica, utilidad pronóstica en la evolución del pie diabético, y utilidad predictiva en el tratamiento vascular del pie diabético respecto a otras pruebas utilizadas en la evaluación del estado vascular del paciente, principalmente el ITB. METODOLOGÍA Se ha realizado una revisión sistemática con el fin de identificar estudios que dieran respuestaal objetivo del presente informe. Se incluyeron estudios que hubieran evaluado la medición de TcPO2 en pacientes con DM sin complicaciones o con pie diabético y hubieran comparado sus resultados con el ITB, el índice dedo-brazo, la palpación de pulsos, la arteriografía, la angioRMN o la angioTAC. Como diseños de estudio, se consideraron revisiones sistemáticas con metanálisis (RSMA), ensayos clínicos, estudios cuasiexperimentales, estudios comparativos, estudios de prueba diagnóstica, estudios de cohortes y estudios de casos y controles. La fecha de la búsqueda fue 10 de noviembre de 2021, sin restricciones en cuanto al periodo temporal. RESULTADOS Se identificaron un total de 573 referencias. Tras la revisión por título y resumen, se seleccionaron 123 referencias, de las cuales 111 no cumplieron con los criterios de inclusión. Finalmente, doce estudios fueron considerados para la síntesis de la evidencia: una RSMA de estudios observacionales y once estudios observacionales no incluidos en dicha revisión. Globalmente, la calidad de los estudios identificados fue considerada incierta o baja. Dos estudios observacionales aportaron resultados en relación con los resultados de seguridad y validez diagnóstica de EAP de la medida de TcPO2 . Uno de ellos se realizó en el ámbito de la atención primaria en pacientes con DM sin complicaciones. Se observaron diferencias significativas en la tasa de diagnosticados con EAP entre diferentes pruebas no invasivas, que fue mayor con el ITB (70%) seguido del IDB (57%), la medida de TcPO2 (30%) y la palpación de pulsos (23%). En pacientes con úlcera, un estudio observacional comunicó los valores predictivos (VPP y VPN) en la identificación de la EAP para el ITB (0,45 y 0,79), para el IDB (0,45, 0,73) y para la TcPO2 (0,28, 0,66). La sensibilidad y especificidad fueron del 68% y 59% para el ITB, del 89% y 45% para el IDB y del 28% y 66% para la medida de TcPO2 . La mayoría de los estudios presentaron resultados de utilidad pronóstica de la TcPO2 en el manejo del pie diabético. La RSMA incluida mostró una sensibilidad y especificidad para la curación de la úlcera del 72% y 86% con la medida de TcPO2 (30 mmHg) y del 48% y 52% con el ITB (0,8). Sus resultados de sensibilidad y especificidad para la amputación fueron de 52% y de 73% con el ITB y de 75% y 58% con la TcPO2 , respectivamente. Algunos de los estudios individuales aportaron resultados de curación de úlcera y amputación con diferentes puntos de corte que obtuvieron resultados heterogéneos de sensibilidad y especificidad de la TcPO2 . Un único estudio mostró la utilidad pronóstica de la TcPO2 sobre la mortalidad, asociando una TcPO2 < 25 mmHg a una mayor tasa de mortalidad a un año. Los resultados sobre la utilidad predictiva de la TcPO2 relacionada con el tratamiento del pie diabético se encontraron en dos estudios observacionales que evaluaron su uso en el procedimiento de revascularización. Tanto los valores de TcPO2 como el resultado del ITB mostraron cambios significativos después de la intervención. No obstante, el ITB no pudo realizarse en el 42% y el 15% de los pacientes incluidos en los respectivos estudios debido a las siguientes causas: por no obtener ninguna señal, no poder comprimirse la arteria o por la existencia de calcificaciones en la capa media arterial. CONCLUSIONES Globalmente, la evidencia identificada sobre el uso de la TcPO2 en el manejo del pie diabético es de calidad incierta o baja. Los resultados de seguridad y la validez diagnóstica de la TcPO2 en pacientes con DM sin complicaciones o pie diabético no son concluyentes. La mayor evidencia se encuentra en el uso de la TcPO2 en el pronóstico de curación de úlceras y amputación en pacientes con pie diabético, y es sugestiva de que la medida de TcPO2 es superior al ITB. La mejor precisión de la TcPO2 indicativa de curación de la úlcera se encuentra en el punto de corte 22,5-28,5 mmHg. Sin embargo, hay incertidumbre acerca del punto de corte de la TcPO2 asociado a un mayor riesgo de amputación. Algunos estudios sugieren que el aumento observado en la TcPO2 después de un procedimiento de revascularización presentaría una mayor sensibilidad y especificidad respecto del ITB.

BACKGROUND/INTRODUCTION The leading cause of complications and hospitalization in patients with diabetes mellitus (DM) is the diabetic foot, defined as a syndrome causing ulceration, infection or gangrene of the foot associated with diabetic neuropathy and varying degrees of peripheral arterial disease (PAD). About 25% of people with DM are at risk of developing a foot ulcer, which can lead to lower limb amputation and a loss of quality of life for patients, and high healthcare costs. PAD occurs in 50% of cases of DM and is associated with ulceration, lower limb amputation, cardiovascular events and increased risk of death. Therefore, the identification and assessment of PAD plays a major role in the management of patients with DM and diabetic foot. Considering the needs of the diabetic foot management, we need technologies to: a) identify PAD in patients with DM, b) predict the evolution of the diabetic foot, and c) select and monitor the vascular treatment of the diabetic foot. Currently, several non-invasive tests are used to diagnose and monitor PAD and to classify the risk of ulceration. One of the most widely used is the ankle-brachial index (ABI). However, it has been suggested that this method has some limitations, especially in patients with calcified arteries. For this reason, the use of transcutaneous partial pressure of oxygen (TcPO2 ) measurement has been proposed. TcPO2 devices are technologies that use a non-invasive electrode to estimate the partial pressure of oxygen at the skin surface and report the oxygen supply from the underlying microvascular circulation. The overall aim of this report is to evaluate the use of TcPO2 measurement in diabetic foot management and to compare its safety, diagnostic validity, prognostic utility in diabetic foot outcomes, and predictive utility in diabetic foot vascular management with other tests used to assess the patient's vascular status, primarily ABI. METHODOLOGY A systematic review was conducted to identify studies that addressed the objective of this report. We included studies that had evaluated TcPO2 measurement in patients with uncomplicated DM or diabetic foot and compared their results with ABI, finger-arm index, pulse palpation, arteriography, MR angiography or CT angiography. Study designs included 26 INFORMES, ESTUDIOS E INVESTIGACIÓN systematic reviews with meta-analyses (SRMAs), clinical trials, cohort studies and case-control studies. The search date was 10 November 2021, with no time restrictions. RESULTS We identified 573 references. After title and abstract screening, we selected 123 references, of which 111 did not meet the inclusion criteria. Finally, 12 studies were included in the evidence synthesis: one SRMA of observational studies and 11 observational studies not included in this review. The quality of the identified studies was considered uncertain or low. Two observational studies provided results on the safety and diagnostic validity of TcPO2 measurement for PAD. One of these was conducted in a primary care setting in patients with uncomplicated DM. Significant differences were observed in the rate of diagnosis of PAD between different non-invasive tests, which was higher for ABI (70%), followed by digit-brachial index (57%), TcPO2 (30%), and pulse palpation (23%). In patients with ulceration, an observational study reported the predictive values (PPV and NPV) of ABI (0.45 y 0.79), digit-brachial index (0.45, 0.73), and TcPO2 (0.28, 0.66) to detect PAD. Sensitivity and specificity were 68% and 59% for ABI, 89% and 45% for digit-brachial index, and 28% and 66% for TcPO2 . Most studies presented results on the prognostic utility of TcPO2 for diabetic foot management. The included SRMA showed sensitivity and specificity results for ulcer healing of 72% and 86% with TcPO2 (30 mmHg), and 48% and 52% with ABI (0.8). The sensitivity and specificity results for amputation were 52% and 73% with ABI, and 75% and 58% with TcPO2 . Some individual studies reported ulcer healing and amputation results with different cut-off points, resulting in heterogeneous sensitivity and specificity results for TcPO2 . A single study showed the prognostic utility of TcPO2 for mortality, with a TcPO2 < 25 mmHg associated with a higher one-year mortality rate. Two observational studies assessing the use of TcPO2 in revascularization procedures provided results on the predictive utility of TcPO2 in diabetic foot management. Both TcPO2 values and ABI score showed significant changes after the procedure. However, ABI could not be not used in some patients (42% and 15%, respectively). CONCLUSIONS Overall, the evidence identified for the use of TcPO2 in the management of the diabetic foot is of uncertain or low quality. The safety results and diagnostic validity of TcPO2 in patients with uncomplicated DM or diabetic foot are inconclusive. The strongest evidence is found for the use of TcPO2 in the prognosis of ulcer healing and amputation in patients with diabetic foot, suggesting that the TcPO2 measurement may be superior to ABI. The best accuracy of TcPO2 as an indicator of ulcer healing is at the cut-off point of 22.5-28.5 mmHg. However, there is uncertainty about the TcPO2 cut-off point associated with an increased risk of amputation. Some studies suggest that the increase in TcPO2 observed after revascularization may have a higher sensitivity and specificity than ABI.

Propolis as an Adjuvant in the Healing of Human Diabetic Foot Wounds Receiving Care in the Diagnostic and Treatment Centre from the Regional Hospital of Talca.

OBJECTIVE: Diabetic foot wounds are a relevant diabetes complication and a major health problem. It has been described that propolis has health benefits due to its anti-inflammatory, antioxidant, and support in the healing process. The current study assessed the effect of propolis as an adjuvant in the healing of human diabetic foot ulcers. This was evaluated in a randomized placebo-controlled study of subjects receiving care in the Diagnostic and Treatment Centre from the Regional Hospital of Talca, Chile. RESEARCH DESIGN AND METHODS: Randomized subjects received ambulatory healing treatment for diabetes foot wounds with propolis spray (3%), which was applied to cover the entire wound surface each time it was dressed from week 0 until cicatrization or 8 weeks as a maximum. Two serum samples were taken (day 0 and end of the study) for cytokine and oxidative stress analyses. Also, macro- and microscopy were analyzed in the process of wound healing. RESULTS: The study comprised 31 subjects with type 2 diabetes in treatment for diabetic foot wounds in the Diagnostic and Treatment Centre from the Regional Hospital of Talca. Propolis promotes a reduction of the wound's area by an average of 4 cm2, related to an increase in the connective tissue deposit compared to the control. Also, propolis increased the glutathione (GSH) and GSH/glutathione disulfide (GSSG) ratio (p < 0.02), depleted tumor necrosis factor- (TNF-) α, and increased interleukin- (IL-) 10 levels. Topical propolis did not modify the biochemical parameters in the serum of the studied subjects. CONCLUSIONS: The topical use of propolis turned out to be an interesting therapeutic strategy as an adjuvant in the care of diabetes foot wounds due to its ability to improve and promote healing based on its anti-inflammatory and antioxidant profile. This trial is registered with NCT03649243.

Diabetic foot ulcer carries high amputation and mortality rates, particularly in the presence of advanced age, peripheral artery disease and anemia.

INTRODUCTION: Foot ulcer is also a clinical marker for limb amputation and for death in diabetic patients. The purpose of this study was to determine amputation and mortality rates and its associated factors in patients with diabetic foot ulcerations in a tertiary hospital in Brazil. METHODS: Retrospective medical records from 654 diabetic foot patients were reviewed. The risk factors were determined using the conditional logistic regression model analysis. RESULTS: The mean patient age was 63.1 years (SD 12.20). Peripheral arterial disease was present in 160 patients (24.5%). Major amputations were performed in 135 (21%). The in-hospital mortality rate was 12% and the mortality rate of the amputees was 22.2%. The lowest hemoglobin level, the median value was 9.50g/dL, (4.0-17.0). Anemia was detected in 89.6% of patients submitted to amputation and in 82,1% of those who died. Hemoglobin <11g/dL was the most significant risk factor for major amputation (odds ratio 5.57, p<0.0001). The presence of peripheral arterial disease and old age were also a risk for major amputation (odds ratio 1.84, p=0.007 and 1.02, p=0.028, respectively). Factors associated with increased risk for death were hemoglobin <11g/dL (odds ratio 4.04, p<0.001), major amputation (1.79, p=0.03) and old age (1.05, p<0,001). CONCLUSIONS: Diabetic foot ulcer is associated with high amputation and mortality rates. Old age, peripheral arterial disease and low hemoglobin level are risk factor for major amputation. Old age, major amputation and low hemoglobin level are risk factors for death.

The economic impact of hospitalization for diabetic foot infections in a Caribbean nation.

CONTEXT: Foot infection is the most common complication of diabetes mellitus in the Caribbean. Diabetic foot infections place a heavy burden on health care resources in the Caribbean. OBJECTIVE: To evaluate the treatment-related costs for diabetic foot infections in a Caribbean nation. METHODS: We identified all patients with diabetic foot infections in a 730-bed hospital serving a catchment population of approximately 400,000 persons from June 1, 2011 through July 31, 2012. The following data were collected: details of infection, antibiotic usage, investigations performed, number of physician consultations, details of operative treatment, and duration of hospitalization. Total charges were tallied to determine the final cost for inhospital treatment of diabetic foot infections. RESULTS: There were 446 patients hospitalized with diabetic foot infections, yielding approximately 0.75% annual risk for patients with diabetes to develop foot infections. The mean duration of hospitalization was 22.5 days. Sixteen patients (3.6%) were treated conservatively without an operative procedure and 430 (96.4%) required some form of operative intervention. There were 885 debridements, 193 minor amputations and 60 major amputations, 7102 wound dressings, 2763 wound cultures, and 27,015 glucometer measurements. When the hospital charges were tallied, a total of US $13,922,178 (mean, US $31,216) were spent to treat diabetic foot infections in these 446 patients during 1 year at this hospital. CONCLUSIONS: Each year, the government of Trinidad and Tobago spends US $85 million, or 0.4% of their gross domestic product, solely to treat patients hospitalized for diabetic foot infections. With this level of national expenditure and the anticipated increase in the prevalence of diabetes, it is necessary to revive the call for investment in preventive public health strategies.

[Ankle-brachial index associated with diabetic foot: case-control study]. / Índice tobillo-brazo asociado a pie diabético. Estudio de casos y ontroles.

INTRODUCTION: The diabetic foot has been associated with substantial morbidity and mortality in diabetic patients. The ankle-brachial index is a simple diagnostic method for peripheral arterial disease. OBJECTIVE: to evaluate the usefulness of the physical ankle-brachial index and known risk factors in the development of diabetic foot. METHODS: In a case-control study, we studied 60 diabetic patients between 20 and 70 years old who were divided according to the presence of diabetic foot (cases); controls were assigned for patients without injury to their feet or other morbidities. The variables studied included: glucose, cholesterol, triglycerides, body mass index, blood pressure, ankle-brachial index, physical exercise, smoking, and alcoholism. RESULTS: Mean age was 55 years for cases and 56 for controls (p = 0.548), with an average of disease progression 15 years for both groups. No differences in metabolic variables were found. A history of smoking (OR = 4.8, 95% CI = 1.50 to 15.80, p = 0,006) and an ankle-brachial index = 0.9 left (OR = 10.6, 95% CI = 1.80 to 55.60, p = 0.004) or right (OR = 5.2, 95% = 1.16 to 24.00, p = 0.049) were associated with development of peripheral arterial disease. Instead, the exercise proved to be a protective factor. CONCLUSIONS: The ankle-brachial index, should be used in primary care clinics for the study of the arterial circulation of the lower limbs, especially in patients with diabetes mellitus of medium and long evolution or cardiovascular risk factors.

Periodontal disease and risk for neuropathic foot ulceration in type 2 diabetes.

AIMS: Diabetic neuropathy (DN) has been associated with oral dryness, tooth loss and an increased risk for foot ulceration, but the association between periodontal problems and DN has not been fully elucidated. This study investigated whether the risk for neuropathic foot ulceration (DM-NFUR) was associated with periodontal disease (PD) in patients with type 2 diabetes mellitus. METHODS: This cross-sectional study examined 122 patients with type 2 diabetes for PD; findings were compared with results for presence of DM-NFUR. PD severity was classified as none/mild (NM-PD), moderate/severe (MS-PD) and edentulous (E). RESULTS: NM-PD was found in 40.2% patients; MS-PD, in 32.0%; and 27.8% were edentulous. DM-NFUR was detected in 18.4% of the patients in the NM-PD group, in 68.2% in the MS-PD group, and in 61.8% of completely edentulous individuals. PD was significantly correlated with DM-NFUR (p

[Analysis of factors associated with extremity ulceration in diabetic subjects with peripheral neuropathy]. / Análise de fatores associados à ulceração de extremidades em indivíduos diabéticos com neuropatia periférica.

Peripheral neuropathy is the main risk factor for foot ulceration in diabetic subjects. This study examined the association of peripheral arterial disease (PAD) with foot ulceration in a sample of diabetic subjects with peripheral neuropathy, and also if inflammatory markers would be associated with this event. We evaluated 32 type 2 diabetic individuals with abnormal 10-g monofilament exam, who were stratified in 2 groups according to history or presence of lower extremities ulcer. The group "with ulcer" (n = 18) included the ones that had active or cicatrized ulcer, or some lower-extremity amputation due to ulcer complications. In addition to the neurological examination and monofilament test, they were submitted to biothesiometry, lower extremity vascular assessment with Doppler, and laboratory determinations. No difference between the groups was found concerning sex distribution, mean age, and duration of diabetes diagnosis. The group with ulcer showed higher mean values of height (1.70 +/- 0.06 vs. 1.63 +/- 0.11 m, p = 0.044), vibration perception threshold measured in medial malleolli (40.9 +/- 13.0 vs. 30.6 +/-12.3 V, p = 0.040) than the group without ulcer. The groups did not differ regarding the mean values of the inflammatory markers. Response to patellae reflex was worse in the group with ulcer (p = 0.047), in which a higher proportion of individuals with abnormal toe-brachial index (p = 0.030) was observed as compared to those without ulcer. We concluded that PAD is associated with the presence of ulcer in neuropathic subjects. The assessment of digital arteries flow in lower limbs (in great toe) contributed to detect such association. Association of diabetic foot ulcers and inflammatory markers was not observed, but cannot be excluded due to limitations of sample size. Prospective studies should examine the sensitivity of the toe-brachial index to identify PAD in diabetic individual at risk of ulceration.

Análise de fatores associados à ulceração de extremidades em indivíduos diabéticos com neuropatia periférica / Analysis of factors associated with extremity ulceration in diabetic subjects with peripheral neuropathy

A neuropatia periférica é o principal fator de risco para ulceração em pé de indivíduos diabéticos. Este estudo testou a associação de doença arterial periférica (DAP) à ulceração do pé em amostra de pacientes com neuropatia sensório-motora simétrica distal e se marcadores inflamatórios subclínicos também se associariam a esse evento. Foram avaliados 32 indivíduos diabéticos tipo 2 com exame do monofilamento de 10 g alterado, estratificados em 2 grupos segundo a história ou presença de úlcera nas extremidades inferiores. O grupo "com úlcera" (n = 18) incluiu aqueles que apresentavam úlcera ativa ou cicatrizada, ou que tiveram alguma amputação em membro inferior decorrente de complicações da úlcera. Além do exame neurológico e monofilamento, foram submetidos a bioestesiometria, avaliação vascular com Doppler e exames laboratoriais. Os grupos foram semelhantes quanto à distribuição dos sexos, média de idade e tempo de diabetes. O grupo com úlcera apresentou valores médios de altura (1,70 ± 0,06 vs. 1,63 ± 0,11 m; p = 0,044) e limiar de percepção vibratória no maléolo medial (40,9 ± 13,0 vs. 30,6 ± 12,3 V; p = 0,040) mais elevados que o sem a úlcera. Os grupos não diferiram entre si quanto à média dos marcadores inflamatórios. A resposta do reflexo patelar foi também pior no grupo com úlcera (p = 0,047), no qual se observou maior proporção de indivíduos com o índice hálux-braquial alterado (p = 0,030) quando comparado ao sem úlcera. Conclui-se que a DAP está associada à presença de úlcera (atual ou pregressa) em membros inferiores de indivíduos diabéticos neuropatas. A pesquisa de alteração de fluxo de artérias digitais de membro inferior (no hálux) contribuiu para detectar tal associação. Associação de neuropatia ulcerada a marcadores inflamatórios não foi observada, não sendo possível excluí-la devido às limitações do tamanho da amostra. Estudos prospectivos deverão examinar a sensibilidade do índice hálux-braquial...

Peripheral neuropathy is the main risk factor for foot ulceration in diabetic subjects. This study examined the association of peripheral arterial disease (PAD) with foot ulceration in a sample of diabetic subjects with peripheral neuropathy, and also if inflammatory markers would be associated with this event. We evaluated 32 type 2 diabetic individuals with abnormal 10-g monofilament exam, who were stratified in 2 groups according to history or presence of lower extremities ulcer. The group "with ulcer" (n = 18) included the ones that had active or cicatrized ulcer, or some lower-extremity amputation due to ulcer complications. In addition to the neurological examination and monofilament test, they were submitted to biothesiometry, lower extremity vascular assessment with Doppler, and laboratory determinations. No difference between the groups was found concerning sex distribution, mean age, and duration of diabetes diagnosis. The group with ulcer showed higher mean values of height (1.70 ± 0.06 vs. 1.63 ± 0.11 m, p = 0.044), vibration perception threshold measured in medial malleolli (40.9 ± 13.0 vs. 30.6 ± 12.3 V, p = 0.040) than the group without ulcer. The groups did not differ regarding the mean values of the inflammatory markers. Response to patellae reflex was worse in the group with ulcer (p = 0.047), in which a higher proportion of individuals with abnormal toe-brachial index (p = 0.030) was observed as compared to those without ulcer. We concluded that PAD is associated with the presence of ulcer in neuropathic subjects. The assessment of digital arteries flow in lower limbs (in great toe) contributed to detect such association. Association of diabetic foot ulcers and inflammatory markers was not observed, but cannot be excluded due to limitations of sample size. Prospective studies should examine the sensitivity of the toe-brachial index to identify PAD in diabetic individual at risk of ulceration.

Glycaemic control influences peripheral blood flow and haemorheological variables in patients with diabetes mellitus.

Since persistent uncontrolled hyperglycaemia predisposes to vascular complications in diabetics, this study aimed at assessing the relationship of glycaemic control to plasma fibrinogen concentration, relative plasma viscosity and ankle arterial blood flow in diabetic patients with (N = 28) and without neuropathy (N = 34) compared with non-diabetic controls (N = 21). Glycaemic control was determined by total glycated haemoglobin (GHb) levels. Patients were placed into three categories of glycaemic control, namely good (GHb 4 -< 8%), fair (GHb 8-12%) and poor (GHb > 12%).Compared with non-diabetics, blood flow was significantly higher (p < 0.05) in patients with good but not poor glycaemic control. Fibrinogen was significantly higher in patients with fair and poor glycaemic control than in non-diabetic subjects (p < 0.05). In non-neuropathic patients, viscosity was higher (p < 0.05) in those with fair control and significantly different (p < 0.05) between those with fair and poor control. The results suggest that the initial vasodilatation in the periphery is attenuated by poor glycaemic control, contributing to the decrease in ankle arterial blood flow as a consequence of the simultaneous increase in plasma fibrinogen and viscosity. These adverse changes may contribute to the development of the diabetic foot.

Healing of diabetic foot ulcers in L-arginine-treated patients.

Experimentally, we demonstrated the beneficial effects of L-arginine on regulation of hyperglycemia and dyslipidemia in experimental diabetes, in addition to a positive anti-aggregating effect in platelets in animals and humans. Here, the effect of L-arginine on foot ulcers from diabetic patients was studied. Three groups of diabetic patients were included: 11 patients without ulcer received neither treatment and served as controls. Eleven patients with diabetic ulcer received the standard treatment, this group served as diabetic control with diabetic ulcer. Eleven remain patients with diabetic ulcer received 10 mM L-arginine subcutaneously on the site of the wound. Biopsy with punch number 5 on wound site comprising both ulcerative and contiguous undamaged skin were performed in all patients with ulcerative lesions before any treatment. Patients with intact skin had biopsy performed with punch number 5 on external malleolar region of right lower limb. Biopsies were examined by light and confocal microscopy utilizing histochemical and immunohistochemical methods. Initial and final blood samples were collected to determine glucose, triglycerides, total cholesterol, glycated hemoglobin (HbA(1c)), low (LDL), and high density lipoproteins (HDL). Significant differences (P < 0.05) were observed between initial and final serum glucose levels for treated patients, and initial serum glucose levels between treated and control patients without diabetic ulcer. Glycated hemoglobin, triglycerides, cholesterol, and lipoprotein levels showed no significant changes. Eight patients treated with L-arginine reached total wound healing and the remaining three who abandoned the study because of change of residence showed relevant improvement. Histochemistry and immunohistochemistry methods have shown vascular impairment in both patients with diabetic ulcer (prior to treatment) and control patients without diabetic ulcer. Our observations strongly support efficacy of L-arginine for successful wound healing of diabetic ulcers.

Low serum magnesium levels and foot ulcers in subjects with type 2 diabetes.

BACKGROUND: Hypomagnesemia is associated with the development of neuropathy and abnormal platelet activity, both of which are risk factors for the progression of ulcers of the feet. Thus, the aim of this study was to determine the relationship between low serum magnesium and foot ulcer in subjects with type 2 diabetes. METHODS: Thirty-three out-patients with type 2 diabetes and foot ulcers (16 women and 17 men) were compared with a control group of 66 out-patients with type 2 diabetes without foot ulcers (35 women and 31 men), matched by age, diabetes duration, HbA1c, and glycemia. Patients with foot ulcers were included in the study only if a foot ulceration onset not exceeding 2 months was established. Patients diagnosed with reduced renal function, a history of alcohol intake, or as having received magnesium supplementation or diuretics were not included. Serum magnesium was measured by colorimetric method. The relationship between serum magnesium and foot ulcers was assessed by logistic regression. RESULTS: Hypomagnesemia was identified in 31 (93.9%) subjects with foot ulcers, and 49 (73.1%) control subjects, p = 0.02. Subjects with foot ulceration had lower serum magnesium levels (1.48 +/- 0.33) than those in the control group (1.68 +/- 0.32), p <0.001. Logistic regression analysis showed a significant relationship between low serum magnesium levels and foot ulcers (odds ratio [OR] 2.9, CI 95% 1.7-6.8; p = 0.01). CONCLUSIONS: Serum magnesium depletion is present and shows a strong relationship with foot ulcers in subjects with type 2 diabetes and foot ulcers, a relationship not previously reported.

[Diabetic neuropathy: thermal sensation and metabolic control in non-insulin-dependent diabetics]. / Neuropatía diabética: sensibilidad térmica y control metabólico en diabéticos no insulinodependientes.

BACKGROUND: The early detection of peripheral neuropathy in diabetics is important since it is the main risk factor for lower limb trophic lesions in diabetics. AIM: To assess the relationship between feet thermal sensation threshold and metabolic control in ambulatory non-insulin-dependent diabetics. PATIENTS AND METHODS: A random sample of 34 non-insulin-dependent diabetics followed for more than five years in a special clinic, out of 368 patients, was selected. Warmth sensation thresholds were measured in the dorsum of both feet using a MSTP-III thermostimulator. The average value of all glycosylated hemoglobins obtained during the 9.7 +/- 5.3 years of follow up for each patient was calculated. A multiple stepwise regression analysis was performed between thermal sensation as the dependent variable and glycosylated hemoglobin, fasting blood glucose, age and diabetes duration. RESULTS: The regression model disclosed glycosylated hemoglobin as the only independent predictor of warmth sensation threshold (partial r = 0.385; p = 0.043). Fifteen diabetic patients with good metabolic control, defined as those with a mean glycosylated hemoglobin of less than 9.5%, had a warmth sensation threshold of 35.6 +/- 3.7 degrees C, whereas 19 diabetics with a had control (glycosylated hemoglobin > or = 9.5%) had a threshold of 39 +/- 3.8 degrees C (p = 0.017). CONCLUSIONS: In this group of diabetics, there is a relationship between the severity of distal polyneuropathy and the metabolic control, assessed with glycosylated hemoglobin levels.