Spotlight on amputations

Several recent studies looked at lower-extremity amputations (LEAs) among patients with diabetes.

Rates of nontraumatic LEA increased among Medicare beneficiaries with diabetes in recent years, according to a study published by Diabetes Care on July 28. The amputation rate dropped significantly between 2000 and 2009 (from 8.5 to 4.4 per 1,000 diabetes patients) but then started rising, to 4.8 per 1,000 in 2017. Rates were highest among the oldest patients, Black patients, and men. The increases were driven by more toe and foot amputations, while rates of amputations above and below the knee continued to decline, the study found. This suggests the increases may be caused by earlier, smaller amputations to avoid bigger ones later, the authors speculated, noting that increases in survival of patients with diabetes and cost barriers to medication adherence are also potential explanations. They called for increased attention to preventive foot care among patients with diabetes.

Both minor and major LEAs are associated with significantly mortality among diabetes patients, according to an Italian study, published by BMJ Open Diabetes Research & Care on July 19. This population cohort study included 1,053 patients who underwent a first amputation. Mortality rates at one and four years were 33% and 65% in those undergoing major amputations and 18% and 45% with minor amputations, respectively. Older age and chronic renal disease were risk factors for mortality after either type of amputation. Diabetes-related cardiovascular complications also predicted risk of death after minor amputation, while antidepressant drug consumption was associated with mortality after a major amputation. The study authors said that results confirm previous findings of high mortality rates after amputation but that the significance of depression is a new finding. “The study highlights the role of depression as specific risk factor for death in patients with diabetes after major LEA and suggests including its definition and management in strategies to reduce the high mortality rate observed in this group of patients,” they wrote.

The COVID-19 pandemic has affected amputations for diabetic foot ulcers (DFUs), according to two recent studies that compared patients hospitalized in 2019 versus 2020. An Italian study, published by Diabetes Care on July 23, included 38 DFU patients from 2019 and 25 from 2020. In 2020, more patients were admitted as emergencies, and rates of both gangrene (64% vs. 29%, P=0.009) and amputation (60% vs. 18%, P=0.001) were higher. “The COVID-19 lockdown may have had a detrimental impact on amputation risk because of the sudden interruption of DFU care and lower limb preservation pathways, resulting in delayed diagnosis and treatment,” the authors said. A similar Chinese study, published by Diabetes Care on Aug. 7, compared 87 patients hospitalized in 2019 to 44 in 2020. More patients in 2020 presented with severe infection (52.3% vs. 20.7%, P<0.001) and the major amputation rate was 11.4%, compared to 4.6% in 2019 (P=0.162). “This study suggests that the COVID-19 outbreak has had serious and disruptive effects on the delivery of DFU care, in terms of considerable drops in hospitalization and extended periods in treatment,” the authors said.

Finally, two studies found no association between sodium-glucose cotransporter-2 (SGLT-2) inhibitors and risk of LEA. A meta-analysis of six studies, published by Diabetes, Obesity and Metabolism on Aug. 3, included 51,713 patients randomized to either an SGLT2 inhibitor or placebo. A total of 858 underwent LEA, and rates were not significantly different in the treatment versus placebo groups (2.0% vs. 1.3%). The authors concluded that this drug class does not seem to be associated with amputation risk but called for a multicenter study with longer follow-up “to confirm these results and provide guidelines for clinical practice.”

Similar conclusions were drawn from a multicenter observational study in Canada and the U.K., published by Diabetes Care on Aug. 5. It matched more than 200,000 new users of SGLT-2 inhibitors to an equal number of patients starting a dipeptidyl peptidase-4 inhibitor. During a mean follow-up time of 11 months, rates of below-knee amputation were similar at 1.3 and 1.5 per 1,000 person-years, respectively. The results of this and other recent studies provide some reassurance after the CANVAS trial suggested that this drug class was associated with amputations, but “studies with a longer duration of follow-up are needed to assess potential long-term effects,” the authors concluded.