In addition, “about half of all nontraumatic amputations in the western world are attributable to diabetes, and an earlier study showed a 40-fold excess risk of amputations in people with T1D compared with the general population,” they said.

As the risk of lower extremity amputation (LEA) has been mostly studied in populations with type 2 diabetes, the investigators sought to better understand incidence over time and potential risk factors for LEA in patients with T1D.

All study participants were over the age of 18, had T1D, and were listed in the Swedish National Diabetes Register. Cohort data were then linked with several other national health registries to glean information on additional factors.

A total of 46,088 individuals with T1D (45% female) were included in final analyses, with a mean (SD) age of 32.5 (14.5) years. The mean duration of diabetes was 17.2 (14.5) years, and around 14% were smokers. Of the patients included, 1519 (3.3%) underwent amputation over a median follow-up of 12.4 years.

The researchers found:

  • 609 (1.3%) individuals underwent a minor amputation, 585 (1.3%) a major amputation, and 325 (0.7%) both minor and major amputation
  • The standardized incidence for any amputation in 1998-2001 was 2.84 (95% CI, 2.32-3.36) per 1000 person-years and decreased to 1.64 (95% CI, 1.38-1.90) per 1000 person-years in 2017-2019
  • Hyperglycemia and renal dysfunction were the strongest risk factors for amputation, followed by older age, male sex, cardiovascular comorbidities (heart failure, stroke, atrial fibrillation, valve disease), smoking, and hypertension
  • Every 1% increase in glycated hemoglobin was associated with a 78% increased risk of amputation
  • Glycemic control and age- and sex-adjusted renal function improved during the corresponding time period, as amputations decreased
  • The risk of amputation associated with being underweight (body mass index <18.5 kg/m2) was increased while being overweight had a small protective effect; obesity had no significant effect on the risk of any amputation

Overall, “the risk of LEA was substantially reduced over time and the incidence was more than 40% lower during 2017-2019 than during 1998-2001,” the researchers wrote.

“The major reduction occurred during 2014-2019 along with clear improvements in glycemic control and renal function, which were the most prominent risk factors related to LEA.”

Data did not find a statistically significant association between increased low-density lipoprotein cholesterol concentrations and risk of amputation, while increased high-density lipoprotein levels offered a protective effect.

Improvements in amputation rates could be related to an increased focus on risk factor management, advanced treatments to optimize glycemic control, and additional measures used in multidisciplinary diabetes foot clinics, the authors hypothesized.

LEA can lead to reduced quality of life, influences work possibilities for many patients, and has significant short- and long-term impacts on health care costs.

Calling the improved prognosis for amputations, renal complications, and glycemic control over time a “breakthrough in T1D care,” the authors concluded, “our study indicates a shift in the era of diabetes probably due to the more extensive use of modern equipment in glucose-lowering therapy, such as advanced insulin pumps and continuous glucose monitoring devices.”

A lack of data on limb-specific risk factors such as neuropathy or deformities that affect amputation risk marks a limitation to this study. Causal relationships also cannot be drawn.


Hallström S, Svensson A, Pivodic A, et al. Risk factors and incidence over time for lower extremity amputations in people with type 1 diabetes: an observational cohort study of 46, 088 patients from the Swedish national diabetes registry. Diabetologia. Published online September 8, 2021. doi:10.1007/s00125-021-05550-z