Social deprivation modifies the association between incident foot ulceration and mortality in type 1 and type 2 diabetes: a longitudinal study of a primary-care cohort

Foot ulceration is the most common complication in diabetes, with a lifetime risk of 25% [1]. The condition portends significant excess morbidity and mortality in individuals with diabetes, who are already facing reduced life expectancy and an unfavourable prognosis [1‐5]. Established aetiological risk factors for foot ulceration in diabetes are suboptimally controlled diabetes, peripheral neuropathy, peripheral vascular disease, foot deformity and previous foot ulceration [1, 6].

Diabetic foot ulceration is a global public health issue, with a prevalence of 13.0% in North America and 5.1% in Europe [7]. The incidence in Europe is around 2% per year [8]. Costs of care are double those seen in individuals without ulceration [9], with the total cost associated with treatment being as high as €10 billion per year in Europe [8]. The incidence of foot ulcers is 2.2% per annum in the UK, and an average of 6000 people with diabetes each year undergo amputation [10, 11]. The financial burden is significant in terms of both healthcare costs and long-term consequences. The annual UK National Health Service expenditure on diabetes foot-related care in 2010–2011 was estimated to be £580 million (US$748 million), representing around 0.6% of total expenditure [12]. Within 5 years (2014–2015), after accounting for inflation, estimates rose to between £972 million and £1.13 billion (US$1.29–1.50 billion), with two-thirds of these costs spent on care for foot ulceration in primary, community and outpatient settings [13]. Consequently, better precision in understanding the risk calculus in relation to the development of diabetic foot ulcers and the likelihood of death in such individuals will result in reduced health service costs and potential cost savings in the longer term.

Previous epidemiological studies have shown a strong association between socioeconomic disadvantage and the prevalence of diabetes [14, 15]. In the general population, mortality is greater in those from a more disadvantaged socioeconomic situation, principally as a result of cardiovascular disease [16]. In the presence of diabetes, however, mortality rates are significantly greater in individuals who live in relatively deprived areas [17]. Furthermore, depression has been found to be associated with a 2.3-fold increase in mortality vs no depression in individuals with diabetes [18]. Psychological factors other than coded diagnoses are difficult to quantify in epidemiological studies, but are clearly important.

The literature on the association between social deprivation and foot ulceration in individuals with diabetes is inconsistent. Two UK studies have shown no association between socioeconomic disadvantage and foot ulceration [19, 20]. Conversely, one Scottish study considered healthcare accessibility as well as socioeconomic disadvantage in the population and demonstrated evidence of increased foot ulceration in the more disadvantaged areas within Scotland [21]. The Eurodiale study has reported that low health-related quality of life is predictive of major amputation and mortality [22].

Few studies have looked at social disadvantage as an independent risk factor in diabetes foot ulceration and as a risk factor for mortality in those with a foot ulcer. The first aim of this study was to determine whether social deprivation is an independent predictor of foot ulceration in people with diabetes in a population with significantly varying levels of social disadvantage. Second, we tested the hypothesis that foot ulceration and level of social disadvantage independently predict all-cause mortality in individuals with type 2 diabetes.

We examined pseudo-anonymised electronic health records from a retrospective cohort of all men and women aged 16–89 years attending 42 general practices in central and eastern Cheshire, UK. The area is a mixed urban and rural environment with a wide range of socioeconomic situations, from significantly disadvantaged urban areas to highly affluent suburbs. The total population of the geographical area studied was 475,000, and the prevalence of significant social disadvantage (based on multiple measures) was 23%.

Individuals were eligible for inclusion if they had a diagnosis of diabetes prior to cohort entry at 1 January 2004 to allow long-term follow-up and no prior history of foot ulceration. A data search was performed through the centralised data facility afforded by Egton Medical Information Systems (EMIS), a commercial organisation that provides health information for nearly all family practices in Cheshire. Permission for this study was sought from and granted by the local information governance and ethics committees. Informed consent was not required as all data were anonymised.

A total of 13,955 individuals (mean age 69.4 years) with diabetes were included in the analyses (Table 1). Of these, 1370 (9.8%) had type 1 diabetes and 12,585 (90.2%) were diagnosed with type 2 diabetes (Table 2). The incidence of foot ulceration increased with age (β = 4.3, p < 0.001), was more common in the elderly (>70 years old) and in individuals with type 2 compared with type 1 diabetes (8.6% [n = 1081] vs 4.8% [n = 66], χ² = 23.3; p < 0.001). In the full cohort, stratified by sex, the occurrence of foot ulceration rate was similar (508/6011 [8.4%]) in women and men (639/7944, [8.0%]). However, amongst those who developed foot ulceration [n = 1147], a greater proportion were male (55.7% vs 44.3%; male versus female, p = 0.0001; Tables 1 and 2). At baseline, greater proportions of individuals with foot ulceration had hypertension, cerebrovascular disease, peripheral vascular disease and a previous myocardial infarction (all p < 0.01, Table 1). Mean systolic and diastolic blood pressure and levels of creatinine and LDL-cholesterol were greater in the presence of foot ulceration in individuals with type 2 diabetes (Table 2). No differences were observed in type 1 diabetes for these covariates.

In this retrospective cohort followed for 10.5 years, individuals with diabetes-related foot ulceration had a higher risk of all-cause mortality than those without a history of foot ulceration. Specifically, after multivariable adjustment, a 48% increased risk of mortality was observed in those who developed a foot ulcer. We also found that social deprivation is an independent predictor of mortality, with the risk of death increasing by 13% per quintile of deprivation (HR 1.13 [95% CI 1.10, 1.17]) independent of baseline age, sex, diabetes type, smoking status, hypertension, statin, β-blocker or metformin use, HbA_1c level and insulin use. Individuals in the highest quintile of deprivation were 77% more likely to develop a foot ulcer compared with those in the lowest quintile.

Our finding demonstrate similar rates of foot ulcer incidence by sex (8.4% vs 8.0%, females vs males). The lower rates of foot ulceration seen here compared with previous studies may relate to the emphasis placed on foot screening and ulceration-preventative measures among individuals with diabetes in the Cheshire and High Peak Derbyshire areas of the UK over the duration of this study. Overall, our findings from real-world electronic medical records are comparable with those of previous epidemiological reports and add to the current body of evidence. The increased mortality reported here is consistent with previous reports [28‐30], including a meta-analysis of 17,830 individuals with diabetes and with or without foot ulceration [31]. This included six prospective [32‐37] and two retrospective cohorts [38, 39].

In the context of social disadvantage, Leese et al, in a Scottish study, showed a link between social disadvantage and diabetic foot disease [21], with the most deprived quintile having a 1.7-fold increased risk of developing a foot ulcer. Access to a GP or hospital clinic was not associated with foot ulceration or amputation. We have previously shown that socially disadvantaged individuals have a predisposition to developing painful peripheral neuropathy, an important determinant of foot ulceration in both type 1 and type 2 diabetes [40]. Regarding the increased death rate in individuals with an established foot ulcer, the dominant prognostic factor may be the effect of social disadvantage [41, 42]. Other factors include a greater intake of foods with a high glycaemic index and concomitant poorer glycaemic control [43].

Among individuals with diabetes, a previous study has reported that both minor and major depression are strongly associated with increased mortality [18]. Specifically, even after adjustment for age, sex, race/ethnicity and educational attainment, compared with the non-depressed group, minor and major depression were associated with a 1.67- and 2.30-fold increase in mortality, respectively. Depression itself was associated with greater socioeconomic disadvantage and lower educational attainment.

The current study has several strengths and weaknesses. It was a longitudinal study of all individuals attending GP practices in Cheshire, UK, with a median follow-up of 10.5 years. As a far as possible, GPs and practice nurses record any events and changes in medication. The area has a stable population, with little migration out of the area. One weakness is that, akin to all studies using primary-care data, our findings are subject to variability in the data entry of different GP practices. In relation to this, a record of more than one episode of foot ulceration could not be ascribed in all cases as true multiple episodes of new foot ulcers. Second, we did not have the actual anatomical location of the foot ulcers. There is potential for under-reporting of foot ulceration. However, the area of the UK included in this study has a highly proactive podiatry service, led by one of the co-authors (GD), that engages closely with GP practices in the diagnosis and treatment of diabetes-related foot problems. Furthermore, diabetes management has changed a lot since 2004, particularly with respect to more aggressive BP and lipid management, with recent studies showing that rates of cardiovascular death have declined. This issue affects prospective studies in this area. Another weakness is that there was no specific information in the GP-coded records on psychological symptoms (including depression), educational attainment and occupation, all of which could potentially affect foot ulceration rates and impact mortality.

Foot problems in diabetes continue to challenge the clinicians who care for these individuals. Not only are foot ulcers associated with morbidity and disability, but they also lead to significant impairment of quality of life [44]. It is known that poor health-related quality of life is a predictive factor for major amputation and mortality [22]. We found increased mortality in individuals with a history of foot ulceration, and this risk increased per quintile of deprivation. This key finding highlights the importance of targeting resources to less socioeconomically advantaged individuals with diabetes in any community, particularly when they have a foot ulcer.

A proactive multidisciplinary approach is warranted to manage foot problems in these individuals. Such an approach should involve actively targeting cardiovascular risk factors at the GP practice level using case identification. This may reduce the incidence of foot ulceration and, subsequently, the associated increased mortality. Recognising and reducing the risk of death from associated comorbid conditions can save not only the limb but also, ultimately, a person’s life. The educational attainment of the individual must be considered for them to appreciate the significance of their own diabetic foot ulceration. Data pertaining to educational attainment were not available for our analysis.

In summary, this study confirms the high mortality of individuals with diabetes-related foot ulcers, in addition to the well established associated substantial morbidity and disability. Socioeconomic disadvantage is an independent predictor of mortality in individuals with diabetes with a foot ulcer and of the occurrence of foot ulceration in people with diabetes. This highlights the importance of taking socioeconomic disadvantage into account when planning future diabetes services.