Incidence of diabetic foot ulcer in Japanese patients with type 2 diabetes mellitus: The Fukuoka diabetes registry

https://doi.org/10.1016/j.diabres.2018.01.020Get rights and content

Abstract

Aims

Although diabetic foot ulcer (DFU) is a serious diabetic complication, there have been no large-scale epidemiological studies of DFU in Japan. We prospectively investigated the incidences of DFU and limb amputation, the risk for developing DFU, and mortality in Japanese patients with type 2 diabetes.

Methods

We followed 4870 participants (mean age, 65 years) with type 2 diabetes attending an outpatient diabetes clinic for a median of 5.3 years (follow-up rate, 97.7%). The primary outcome was the development of DFU.

Results

During the follow-up period, DFU occurred in 74 participants (incidence rate, 2.9/1000 person-years) and limb amputation in 12 (incidence rate, 0.47/1000 person-years). DFU recurrence was observed in 21.4% of participants with history of DFU. History of DFU, chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2), depressive symptoms, and poor glycemic control were significant risk factors for developing DFU. Survival was significantly lower in participants with DFU and/or history of DFU compared with those without (5-year survival rates: with DFU, 87.7%, without DFU, 95.3%; P < .0001). The hazard ratio for death was 1.80 (95% confidence interval, 1.13–2.73, P = .014) in those with DFU and/or history of DFU in a multi-adjusted model. The most common cause of death was cardiovascular disease among participants with DFU, whereas it was malignant neoplasm among those without.

Conclusions

Incidences of DFU and limb amputation were 0.3% and 0.05% per year in this Japanese cohort, respectively. Mortality significantly increased approximately 2-fold in those with DFU and/or history of DFU compared with those without.

Introduction

The number of people with type 2 diabetes mellitus is increasing globally, and chronic diabetic complications are a serious health concern as well as an economic burden [1]. Among complications, diabetic foot ulcer (DFU) can result in limb amputation and contributes to the morbidity and mortality of patients with diabetes mellitus [2]. The International Working Group on the Diabetic Foot reported an estimated annual incidence of DFU of approximately 2%, and a lifetime incidence lies between 15 and 25% [3]. Recurrence of DFU is also common, with reported rates of 30–40% within 1 year after DFU healing [3]. However, a recent meta-analysis reported that the prevalence of DFU varies considerably by country [4] and studied populations [5], although epidemiological studies form the backbone of health strategies in certain areas of the world.

In Japan, the 2016 National Health and Nutrition Examination Survey revealed that 12.1% of adults had diabetes mellitus (defined as HbA1c ≥6.5%) or were undergoing treatment for diabetes [6]. Although the prevalence of DFU was 2% in a national survey conducted in 1990 [7], to our knowledge, there have been no large-scale epidemiological studies on the incidence of DFU since then. In the current study, we prospectively investigated the incidences of DFU and limb amputation, the risk for developing DFU, and mortality in Japanese patients with type 2 diabetes.

Section snippets

Participants

The Fukuoka Diabetes Registry is a multicenter prospective study designed to investigate the influence of modern treatments on the prognoses of patients with diabetes mellitus. The registry includes patients who regularly attend teaching hospitals certified by the Japan Diabetes Society or certified diabetes clinics in Fukuoka Prefecture, Japan (UMIN Clinical Trial Registry 000002627) [8]. A total of 5131 patients with diabetes mellitus aged 20 years or older were registered between April 2008

Baseline characteristics

DFU developed in 74 participants during the follow-up period (n = 4870; median follow-up period, 5.4 years; follow-up rate, 97.7%). Baseline characteristics of participants are shown in Table 1. Participants who developed DFU had a longer duration of diabetes, less LTPA, higher prevalence of depressive symptoms, poor glycemic control, insulin therapy, antihypertensive use, eGFR <60 mL/min/1.73 m2, eGFR <30 mL/min/1.73 m2, history of DFU, history of limb amputation, PAD, and CVD, and lower LDL

Comparison with other studies

We found that the incidences of DFU and limb amputation were 0.3% and 0.05% per year, respectively, in this cohort of Japanese patients with type 2 diabetes. This is the first large-scale prospective study to our knowledge to investigate the incidences of DFU and amputation in Japan. The annual incidence of DFU was reported to be 1.9% in the US (n = 8965, without history of DFU for the previous 1 year) [12], 2.1% in the Netherlands (n = 665) [13], 2.2% in the UK (n = 9710, including 2.8% with

Conflict of interest

No conflicting relationship exists for any author.

Financial disclosures

This work was supported, in part, by the Japan Society for the Promotion of Science KAKENHI (Grant Nos. 23249037 and 23659353 to M.I.; and 16 K00861 to H.F.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Contribution statement

M.I. was responsible for the study concept and design. M.I. and H.F. conducted the analysis. U.N., T.O., H.I., T.J-K., A.S., Y.M., M.Y., and T.K. interpreted the data and contributed to the discussion. M.I. drafted the manuscript. All authors participated in critically revising the manuscript and approved the final version. M.I. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the

Acknowledgments

The authors thank Drs. Yutaka Kiyohara, Yasufumi Doi, Toshiharu Ninomiya, Shigenobu Kanba, Shuzo Kumagai, Shinako Kaizu, Chisa Matsumoto, Chie Kitaoka (Kyushu University), Nobutaka Tsutsu, Nobuhiro Sasaki (Fukuoka Red Cross Hospital), Kiyohide Nunoi, Yuichi Sato, Yuji Uchizono, Ayumi Yamauchi, Kaori Itoh, Chie Kono (St. Mary’s Hospital), Sakae Nohara, Hirofumi Imoto, Kazushi Amano (Steel Memorial Yawata Hospital), Daisuke Gotoh, Toshitaka Himeno, Masae Toyonaga (Kyushu Central Hospital),

References (34)

  • J.J. van Netten et al.

    Prevention of foot ulcers in the at-risk patient with diabetes: a systematic review

    Diabetes Metab Res Rev

    (2016)
  • P. Zhang et al.

    Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis

    Ann Med

    (2017)
  • W.H. van Houtum

    Amputations and ulceration; pitfalls in assessing incidence

    Diabetes Metab Res Rev

    (2008)
  • Ministry of Health, Labour and Welfare http://www.mhlw.go.jp/stf/houdou/0000177189.html;...
  • T. Ohkuma et al.

    Impact of sleep duration on obesity and the glycemic level in patients with type 2 diabetes: the Fukuoka diabetes registry

    Diabetes Care

    (2013)
  • B.E. Ainsworth et al.

    Compendium of physical activities: an update of activity codes and MET intensities

    Med Sci Sports Exerc

    (2000)
  • L.S. Radloff

    The CES-D Scale: a self-report depression scale for research in the general population

    Appl Psychol Meas

    (1977)
  • Cited by (38)

    • Incidence and characteristics of diabetic foot ulcers in subjects with type 2 diabetes in Catalonian primary care centres: An observational multicentre study

      2021, Primary Care Diabetes
      Citation Excerpt :

      These differences are mainly due to the different definitions of diabetic foot, the classification used in each study, the diagnostic codes used for the registration of DFU, and also, very importantly, the level of care where the study was conducted [2]. Large studies have included subjects treated in multidisciplinary foot centres that have studied the characteristics and evolution of DFU [10–14]. However, these studies included subjects with a high prevalence of complicated ulcers.

    • Development and validation of an incidence risk prediction model for early foot ulcer in diabetes based on a high evidence systematic review and meta-analysis

      2021, Diabetes Research and Clinical Practice
      Citation Excerpt :

      3521 studies were excluded after reviewing the titles and abstracts. The full texts of the remaining 52 studies were carefully evaluated, and 20 cohort studies [14–33] were ultimately incorporated in the final analysis. Flow diagram of the literature selection process is shown in Fig. 1.

    View all citing articles on Scopus
    View full text