To Örebro University

Background and aims: Risk factors for lower limb amputation (LLA) in individuals with diabetes have been under-studied. We examined how demographic and socioeconomic, medical and life-style risk factors may be associated with LLA in people with newly diagnosed diabetes.

Materials and methods: We conducted a cohort study using Swedish national register-linked data. We identified, through the Swedish national diabetes register, all individuals 18 years or older with an incident diabetes diagnosis and no previous amputation from 2007 to 2016. These individuals were followed from the date of the diagnosis to amputation, emigration, death, or the end of the study in 2017, whichever occurred first. Several national Swedish registers were used to obtain data on incident LLA and potential risk factors, including demographic and socioeconomic, medical and lifestyle variables. Variables with more than 40% missing data were excluded from the analysis. The cohort consisted of 66,569 individuals, where of 133 hadan amputation. Cox proportional hazards models were used to obtain hazard ratio (HR) with 95% confidence interval (CI) for associations between demographic and socioeconomic, medical and lifestyle vari-ables and amputation risk. Both unadjusted and mutually adjusted models were fitted.

Results: During the median follow-up time of 4 years there were in total 133 LLA. Based on the model mutually adjusting for all variables, higher age, HR 1.08 (95% CI, 1.05 - 1.10) per year, and being divorced compared with being married, HR 1.67 (1.07 - 2.60) showed positive association. Male sex indicated higher risk, HR 1.57 (1.06 - 2.34). Individuals with an increased foot risk at baseline had increased risk for LLA compared to individuals with healthy feet (neuropathy/angiopathy, HR 4.12 (2.84 - 5.98), previous wounds, HR 8.26 (3.29 - 20.74), ongoing severe foot disease, HR 11.24 (4.82 - 26.23). Insulin treatment compared with diet-only treatment showed HR 2.03 (1.10 - 3.74). Hypertension and HbA1c were not statistically significantly associated with LLA risk. People with obesity had a statistically significant lower risk, HR 0.46 (0.29 - 0.75), compared with individuals with normal weight. Smoking was associated with an increased risk compared with no smoking, HR 1.99 (1.28 - 3.09). Finally, low physical activity (<1 time/week) was associated with an increased risk with a HR of 2.05 (1.30 - 3.23) compared with daily physical activity.

Conclusion: This study found a higher risk for LLA among people with higher age, male sex, who were divorced, who had a higher foot risk group, who were on insulin treatment, lower physical activity levels, and who were smoking. Obesity was associated with lower risk for LLA. Thus, these variables may have important roles in LLA risk among individuals with diabetes.