The amputation rate is much lower in Japanese patients with diabetes than in Western populations [2]. Higher HbA1c values represent a major risk factor for amputation, leading to the speculation that effective glycemic control is associated with a lower amputation risk by preventing progression of diabetic neuropathy and/or exacerbation of infection. A study on the frequency of lower limb amputations in a Japanese hospital specializing in diabetes mellitus (average patient age, 65 years) showed a lower limb amputation frequency of 0.47 per 1,000 persons/year [5]. Participants in our analysis were slightly younger (average age, 54 years), and our participants included fewer elderly people; therefore, the lower limb amputation frequency may have been lower.
The prevalence of lower limb amputations has been reported to be higher in diabetic patients than in those without diabetes. A Swedish study showed that the atraumatic lower limb amputation rate was approximately eight times higher in patients with diabetes than in those without diabetes [6]. Additionally, hyperglycemia and HbA1c elevation were shown to be risk factors for lower limb amputation in diabetic patients [7]. A high degree of hyperglycemia is thought to delay wound healing and significantly increase the risk of wound infection after surgery [8]. A 7-year follow-up study of diabetic patients showed that elevated HbA1c was positively correlated with the risk of lower limb amputation and that the frequency of lower limb amputations increased linearly as the glycemic control worsened [9].
In a national nutrition survey conducted from 1999–2000 in the United States, the frequency of lower limb amputations increased with age among diabetic patients [10]. A survey by the Ministry of Health, Labour and Welfare showed that the average life expectancy in Japan in 2015 was 80 years in men and 87 years in women, which is the highest life expectancy ever reported worldwide. With the extended average life expectancy, the proportion of people aged ≥ 65 years in Japan's total population (127.08 million as of October 1, 2014) reached 26.0% (33 million) and is expected to reach 40.0% in 2060. As the population ages, the number of elderly people with diabetes also increases. Data from 2001–2010 showed that the average life expectancy of diabetic patients was 71.4 years for men and 75.1 years for women. This was extended by 3.4 years for men and 3.5 years for women compared with the average life span surveyed from 1991–2000 [11]. As the aging population increases in Japan, China and other Asian countries, the frequency of lower limb amputations may increase in East Asia.
The proportion of lower limb amputations in diabetic patients has decreased by approximately half in the last 20 years [10], possibly owing to better glycemic and lipid control. Although the absolute number of lower limb amputations among diabetic patients has decreased, in our study, the risk of lower limb amputation increased as the HbA1c levels increased. In the UK Prospective Diabetes Study, death due to lower limb amputation and arteriosclerosis obliterans increased as the HbA1c increased. Conversely, each 1% decrease in HbA1c reduces the HR for amputation or death from peripheral vascular disease by 43%. Thus, effective blood glucose control may help reduce the frequency of lower limb amputations [12]. Elderly patients can often tolerate high blood glucose and HbA1c levels; however, their risk of lower limb amputation increases. Therefore, clinicians should carefully observe the conditions of their lower limbs during examinations and provide individualized interventions.
Our analysis did not show smoking as a significant risk factor for lower limb amputation. However, smoking remains a risk factor for cardiovascular events and various cancers [13], and smoking cessation remains important in treating diabetes.
One limitation of this study was that no examinations were performed to check for the presence or absence of lower limb ulcers. The risk of lower limb amputation is considered high in patients with a high frequency of lower limb ulcers.