Gender differences in infected diabetic foot ulcers

NewsBot · Jan 15, 2010

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Infected foot ulcers in male and female diabetic patients: a clinico-bioinformative study.
Shakil S, Khan AU.
Ann Clin Microbiol Antimicrob. 2010 Jan 14;9(1):2.

BACKGROUND: The study aimed at (i) characterizing the mode of transmission of blaCTX-M and blaTEM-1 among extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli strains isolated from infected diabetic foot ulcers, and (ii) identifying the risk factors for "sex-associated multidrug resistant Gram-negative bacterial (MDRGNB)-infection status" of the ulcers.

METHODS: Seventy-seven diabetic patients having clinically infected foot ulcers were studied in a consecutive series. The E. coli strains isolated from the ulcers were screened for blaCTX-M, blaTEM-1, armA, rmtA and rmtB during the 2-year study-period. PCR amplified blaCTX-M genes were cloned and sequenced. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was used for the analysis of genetic relatedness of the ESBL-producers. Risk factors for "sex-associated MDRGNB-infection status" of ulcers were assessed. Modeling was performed using Swiss-Model-Server and verified by Procheck and verify3D programmes. Discovery Studio2.0 (Accelrys) was used to prepare Ramachandran plots. Z-scores were calculated using 'WHAT IF'-package. Docking of cefotaxime with modeled CTX-M-15 enzyme was performed using Hex5.1.

RESULTS: Among 51 E. coli isolates, 14 (27.5%) ESBL-producers were identified. Only 7 Class1 integrons, 2 blaCTX-M-15, and 1 blaTEM-1 were detected. Ceftazidime and cefotaxime resistance markers were present on the plasmidic DNA of both the blaCTX-M-15 positive strains and were transmissible through conjugation. The residues Asn132, Glu166, Pro167, Val172, Lys234 and Thr235 of CTX-M-15 were found to make important contacts with cefotaxime in the docked-complex. Multivariate analysis proved 'Glycemic control at discharge' as the single independent risk factor.

CONCLUSIONS: Male diabetic patients with MDRGNB-infected foot ulcers have poor glycemic control and hence they might have higher mortality rates compared to their female counterparts. Plasmid-mediated conjugal transfer, albeit at a low frequency might be the possible mechanism of transfer of blaCTX-M-15 resistance marker in the present setting. Since the docking results proved that the amino acid residues Asn132, Glu166, Pro167, Val172, Lys234 and Thr235 of CTX-M-15 (enzyme) make important contacts with cefotaxime (drug) in the 'enzyme-drug complex', researchers are expected to duly utilize this information for designing more potent and versatile CTX-M-inhibitors.
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NewsBot · Jul 30, 2020

Gender difference in the risk of adverse outcomes after diabetic foot disease: A mini review
Giuseppe Seghieri et al
Curr Diabetes Rev. 2020 Jul 16

Diabetic foot disease (DFD) is a complication of diabetes mellitus, characterized by multiple pathogenetic factors and bearing a very high burden of disability as well as of direct and indirect costs for individuals or healthcare systems. A further characteristic of DFD is that it is associated with a marked risk of subsequent hospitalizations for incident cardiovascular events, chronic renal failure or of all-cause mortality. Additionally, DFD is strongly linked to the male sex, being much more prevalent among men. However, even if DFD mainly affects males, several past reports suggest that females are disadvantaged as regards the risk of subsequent adverse outcomes. This review aims to clarify this point, attempting to provide an explanation for this apparent oddity: being DFD a typically male complication of diabetes but, seemingly, with a greater load of subsequent consequences for females.
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NewsBot · Jan 24, 2021

The Weakness of the Strong Sex: Differences Between Men and Women Affected by Diabetic Foot Disease
Elisabetta Iacopi et al
Int J Low Extrem Wounds. 2021 Jan 22

We aimed to analyze sex-related differences in clinical outcomes among patients with diabetic foot disease (DFD) managed in a third-level referral center. We retrospectively analyzed data of admissions performed in our department between 2011 and 2015 for DFD. We collected demographic and clinical data, procedures performed during the admission, and short- and long-term outcomes in terms of healing rate and healing time, major amputation, and mortality rates during the follow-up. We focused on differences between genders and tried to figure out if sex could be considered a predictive factor. We collected data from 1237 admission performed in 842 patients (615 men [73%] and 227 women [27%]; age: 68.6 ± 27.9 years; diabetes duration: 16.4 ± 13.4 years; body mass index: 28.2 ± 6.4 kg/m2; hemoglobin A1c 7.9 ± 1.9%). Men showed a higher prevalence of comorbidities and previous ulcers or revascularization procedures. Men had a significantly higher healing rate compared with women (85.4% vs 63.2%, P < .001), but a longer healing time (124 ± 27 days vs 87 ± 14 days, P = .02). Major amputation did not differ between groups, while mortality rate was significantly higher in men (24.5% vs 16.1%, P = .02). In Cox's regression analysis, male sex was a positive predictive factor for healing and a negative one for time to heal and mortality. The difference in mortality was confirmed by a Kaplan-Meier analysis (log rank test: P = .03). DFD represents a severe disease and a strong marker of mortality affecting more severely on clinical outcomes and survival on men.
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NewsBot · Feb 14, 2021

Body Image as a Mediator Between Gender and Quality of Life Among Patients With Diabetic Foot Ulcers in Indonesia
Ni Made Manik Elisa Putri et al
J Transcult Nurs. 2021 Feb 10

Introduction: Foot ulcers cause women in Indonesia to lose opportunities to participate in religious and cultural activities due to the inability to wear certain footwear. This study examined body image as a mediator in the relationship between gender and quality of life (QoL) among patients with diabetic foot ulcer (DFU) in Indonesia.

Method: A cross-sectional design with convenience sampling was used to recruit participants at the Surgical Outpatient Department and Wound Care Clinic in Bali, Indonesia. The Diabetic Foot Ulcer Scale-Short Form and the body image domain of the Body Investment Scale were administered.

Results: We found gender differences in participants' (n = 201) QoL and body image (p < .05). Body image fully mediated the effect of the relationship between gender and QoL (B = 6.68; 95% confidence interval [3.14, 10.52]) and explained 39.13% of the variance.

Discussion: Health care providers should consider patients' religious beliefs in DFU education and consider women's body image issues. Diabetes foot ulcer may prevent women from performing religious rituals, thus, influencing their QoL. Protective strategies to prevent DFU among women in Indonesia warrant further development.
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NewsBot · Aug 31, 2021

Female disadvantage in risk of adverse outcomes after incident diabetic foot hospitalizations: A population cohort study
Giuseppe Seghieri et al
Curr Diabetes Rev. 2021 Aug 27

Background: Diabetic foot disease (DFD) is more prevalent among males and is associated with an excess-risk of cardiovascular events or mortality.

Aims: This study explores the risk of next cardiovascular events, renal failure and all-cause mortality after incident DFD hospitalizations, separately in males and females to detect any gender difference in a cohort of 322,140 persons with diabetes retrospectively followed-up through administrative data-sources in Tuscany, Italy over years 2011-2018.

Methods: The hazard ratio (HR) for incident adverse outcomes after first hospitalizations for DFD categorized as: major/minor amputations (No.=449;3.89%), lower limbs' revascularizations (LLR: No.=2854;24.75%) and lower-extremity-arterial-disease (LEAD) with no procedures (LEAD-no proc: No.=6282;54.49%), was compared to risk of patients with background-DFD (ulcers, infections, Charcot-neuroarthropathy: No.=1,944;16.86%).

Results: DFD incidence-rate was higher among males compared to females [1.57(95% CI:1.54-1.61) vs. 0.97(0.94-1.00)/100,000p-years]. After DFD the overall risk of coronary artery disease was significantly associated to male gender and that of stroke to female gender. LEAD-no proc and LLR were associated with risk of stroke risk only in females and with coronary artery disease at a significantly higher extent among women. Incident renal failure was not associated with any DFD category. Amputations and LEAD-no proc, significantly predicted mortality risk only in females while LLR reduced such risk in both genders. Females had a greater risk of composite outcome (death or cardiovascular events). When compared with background-DFD the risk was by 34% higher after amputations [HR: 1.34(1.04-1.72)] and by 10% higher after LEAD-no proc: [HR:1.10(1.03-1.18)] for LEAD-no proc, overall confirming that after incident DFD more strictly associated with vascular pathogenesis females are burdened by a greater excess-risk of adverse events.

Conclusions: After incident DFD hospitalizations, females with DFD associated with amputations or with arterial disease are burdened by a greater excess risk of subsequent adverse cardiovascular events, compared with those with background DFD.
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NewsBot · Jan 19, 2023

Male or female sex: considerations and translational aspects in diabetic foot ulcer research using rodent models
Vikrant Rai, Devendra K Agrawal
Mol Cell Biochem. 2022 Dec 27

Treatment of nonhealing diabetic foot ulcers (DFUs) is a major clinical concern and challenge for clinicians. Despite the advancement in treatment strategies, there is no definitive treatment for complicated nonhealing DFUs. Animal models are crucial for understanding pathogenesis and investigating novel therapeutic small molecules and the rodent model is commonly used for research related to cutaneous wound healing. Sexual dimorphism and its effect on the efficacy of sex hormones in enhancing healing in cutaneous wounds using a rodent model have been discussed, however, there is a lack of data related to diabetic foot ulcers. Further, the effects of sexual dimorphism on the issues related to induction of diabetes, differential immune response, type and size of the wound, the effectiveness of topical versus systemic treatment, and molecular mechanisms involved in wound healing like hemostasis, granulation tissue formation, the response of keratinocytes and fibroblasts, inflammation, and skin anatomy are scarcely discussed. Understanding these aspects is of significance and will help in choosing the correct sex, species, and strain of rodents while investigating therapeutic small molecules for DFUs. This review critically summarized these issues and their translational aspects followed by highlighting the effect of sexual dimorphism on these important aspects.
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NewsBot · Feb 19, 2023

Sex differences in diabetic foot ulcer severity and outcome in Belgium
An-Sofie Vanherwegen et al
PLoS One. 2023 Feb 16;18(2)

Background: Sex differences are increasingly recognized to play an important role in the epidemiology, treatment and outcomes of many diseases. This study aims to describe differences between sexes in patient characteristics, ulcer severity and outcome after 6 months in individuals with a diabetic foot ulcer (DFU).

Methods: A total of 1,771 patients with moderate to severe DFU participated in a national prospective, multicenter cohort study. Data were collected on demographics, medical history, current DFU and outcome. For data analysis, a Generalized Estimating Equation model and an adjusted Cox proportional hazards regression were used.

Results: The vast majority of patients included were male (72%). Ulcers in men were deeper, more frequently displaying probe to bone, and more frequently deeply infected. Twice as many men presented with systemic infection as women. Men demonstrated a higher prevalence of previous lower limb revascularization, while women presented more frequently with renal insufficiency. Smoking was more common in men than in women. No differences in presentation delay were observed. In the Cox regression analysis, women had a 26% higher chance of healing without major amputation as a first event (hazard ratio 1.258 (95% confidence interval 1.048-1.509)).

Conclusions: Men presented with more severe DFU than women, although no increase in presentation delay was observed. Moreover, female sex was significantly associated with a higher probability of ulcer healing as a first event. Among many possible contributing factors, a worse vascular state associated with a higher rate of (previous) smoking in men stands out.
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NewsBot · May 14, 2023

Metrics of Gender Differences in Mortality Risk after Diabetic Foot Disease
Giuseppe Seghieri et al
J Clin Med. 2023 May 5;12(9):3288

Background: The aim of this study was to clarify any gender differences in the mortality risk of people with DFD since patients with diabetic foot disease (DFD) are at a high risk of mortality and, at the same time, are more likely to be men.

Methods: From regional administrative sources, the survival probability was retrospectively evaluated by the Kaplan-Meier method and using the Cox proportional-hazards model comparing people with DFD to those without DFD across the years 2011-2018 in Tuscany, Italy. Gender difference in mortality was evaluated by the ratio of hazard ratios (RHR) of men to women after initial DFD hospitalizations (n = 11,529) or in a cohort with prior history of DFD hospitalizations (n = 11,246).

Results: In both cohorts, the survival probability after DFD was lower among women. Compared to those without DFD, after initial DFD hospitalizations, the mortality risk was significantly (18%) higher for men compared to women. This excess risk was particularly high after major amputations but also after ulcers, infections, gangrene, or Charcot, with a lower reduction after revascularization procedures among men. In the cohort that included people with a history of prior DFD hospitalizations, except for the risk of minor amputations being higher for men, there was no gender difference in mortality risk.

Conclusions: In people with DFD, the overall survival probability was lower among women. Compared to those without DFD after a first DFD hospitalization, men were at higher risk of mortality. This excess risk disappeared in groups with a history of previous DFD hospitalizations containing a greater percentage of women who were older and probably had a longer duration of diabetes and thus becoming, over time, progressively frailer than men.
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