SGLT2 inhibitors for diabetes are linked to increased risk of lower limb amputation

BMJ ◽  
2018 ◽  
pp. k4828 ◽  
Author(s):  
Zosia Kmietowicz
Keyword(s):  
Lower Limb ◽  
Sglt2 Inhibitors ◽  
Lower Limb Amputation ◽  
Limb Amputation ◽  
Increased Risk

scholarly journals Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study

BMJ ◽  
2018 ◽  
pp. k4365 ◽  
Author(s):  
Peter Ueda ◽  
Henrik Svanström ◽  
Mads Melbye ◽  
Björn Eliasson ◽  
Ann-Marie Svensson ◽  
...  
Keyword(s):  
Adverse Events ◽  
Diabetic Ketoacidosis ◽  
Lower Limb ◽  
Kidney Injury ◽  
Sglt2 Inhibitors ◽  
Lower Limb Amputation ◽  
Limb Amputation ◽  
Serious Adverse Events ◽  
Receptor Agonists ◽  
Increased Risk

Abstract Objective To assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern. Design Register based cohort study. Setting Sweden and Denmark from July 2013 to December 2016. Participants A propensity score matched cohort of 17 213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17 213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists. Main outcome measures The primary outcomes were lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis, as identified from hospital records. Hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models. Results Use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation (incidence rate 2.7 v 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 v 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 v 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 v 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 v 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 v 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 v 1.2, 1.16, 0.64 to 2.12). Conclusions In this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern.

Abstract MP14: Proteinuria is Associated With a Greater Risk of Lower Limb Amputation in Patients With Peripheral Artery Disease

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Jung-Im Shin ◽  
Morgan Grams ◽  
Josef Coresh ◽  
Alex Chang ◽  
Kunihiro Matsushita
Keyword(s):  
Peripheral Artery Disease ◽  
Lower Limb ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Lower Limb Amputation ◽  
Limb Amputation ◽  
Antiplatelet Drug ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Introduction: Proteinuria is shown to be associated with increased risk of peripheral artery disease (PAD). However, its association with the risk of lower limb amputation in patients with PAD is unknown. Hypothesis: We hypothesized that proteinuria is associated with the risk of amputation in patients with PAD in a graded fashion. Methods: We identified 3,388 PAD patients with data on urine dipstick proteinuria within two years prior to PAD diagnosis between 1997 and 2017 in the Geisinger Health System (mean age 69.7 years, 44.8% female, 97.4% non-Hispanic White, 57.8% diabetic). We quantified the association of proteinuria with the risk of amputation using Cox proportional hazards models, adjusting for demographics, calendar year, estimated glomerular filtration rate, HbA1c, comorbidities including diabetic retinopathy/neuropathy, and medication use (antiplatelet drug, statin, and renin-angiotensin system inhibitor). Results: There were 55.2% with negative dipstick proteinuria, 11.1% trace, 14.1% with 1+, and 19.5% with ≥2+. A total of 245 patients underwent amputations over a median follow-up of 3.4 years. Incidence rate of amputation was 1.15 per 100 person-years for dipstick negative, 1.47 for trace, 2.11 for 1+, and 3.78 for ≥2+. This dose-response relationship remained similar even after accounting for potential confounders (p-trend=0.015), with particularly evident association for ≥2+ of dipstick (an adjusted hazard ratio of 1.52 [95% confidence interval: 1.08-2.17, p=0.017) (Figure). When we added proteinuria to other covariates, the risk discrimination slightly improved (Δc-statistic 0.007 [0.001-0.014]). Conclusions: Higher proteinuria was associated with a greater risk of lower limb amputation among patients with newly diagnosed PAD. Our results suggest the importance of considering proteinuria in risk assessment of limb loss in PAD patients.

scholarly journals Skin problems of the stump and hand function in lower limb amputees: A historic cohort study

2008 ◽  
Vol 32 (2) ◽  
pp. 179-185 ◽  
Author(s):  
E. C. T. Baars ◽  
P. U. Dijkstra ◽  
J. H. B. Geertzen
Keyword(s):  
Cohort Study ◽  
Lower Limb ◽  
Hand Function ◽  
Study Data ◽  
Lower Limb Amputation ◽  
Limb Amputation ◽  
Amputation Stump ◽  
Increased Risk ◽  
Co Morbidity ◽  
Historic Cohort

The aim of this study was to investigate the relationship between liner-related skin problems of the stump in patients with a lower limb amputation and impaired hand function. Sixty patients who were treated in a rehabilitation hospital from 1998–2006 were included in an historic cohort study. Data were collected concerning the amputation, skin problems of the stump, co-morbidity, hand function, the prosthesis, liner use and mobility score. The study population consisted of 50 trans-tibial and 10 knee disarticulation amputees, 43 male and 17 female, with a mean age of 62.3 years. The majority (63%) had a vascular reason for amputation. Blisters, folliculitis, rash and surface wounds on the stump were operationalized as being liner related. In patients with an impaired hand function, 70% had experienced liner-related skin problems of the stump, whereas 32% of the patients with a normal hand function had experienced skin problems ( p = 0.035). This study shows that impaired hand function poses an increased risk for skin problems in the amputation stump in patients with a lower limb amputation and liner use in their prosthesis.

Trunk Postural Control Strategies Among Persons With Lower-Limb Amputation While Walking and Performing a Concurrent Task

2020 ◽  
pp. 1-6
Author(s):  
Courtney M. Butowicz ◽  
Julian C. Acasio ◽  
Brad D. Hendershot
Keyword(s):  
Postural Control ◽  
Lyapunov Exponents ◽  
Lower Limb ◽  
Local Stability ◽  
Control Strategies ◽  
Concurrent Task ◽  
Lower Limb Amputation ◽  
Limb Amputation ◽  
Increased Risk ◽  
Gait Mechanics

Altered trunk movements during gait in persons with lower-limb amputation are often associated with an increased risk for secondary health conditions; however, the postural control strategies underlying such alterations remain unclear. In this secondary analysis, the authors employed nonlinear measures of triplanar trunk accelerations via short-term Lyapunov exponents to investigate trunk local stability as well as spatiotemporal gait parameters to describe gait mechanics. The authors also evaluated the influence of a concurrent task on trunk local stability and gait mechanics to explore if competition for neuromuscular processing resources can assist in identifying unique strategies to control kinematic variability. Sixteen males with amputation—8 transtibial and 8 transfemoral—and 8 uninjured males (controls) walked on a treadmill at their self-selected speed (mean = 1.2 m/s ±10%) in 5 experimental conditions (8 min each): 4 while performing a concurrent task (2 walking and 2 seated) and 1 with no concurrent task. Individuals with amputation demonstrated significantly smaller Lyapunov exponents than controls in all 3 planes of motion, regardless of concurrent task or level of amputation (P < .0001). Individuals with transfemoral amputation walked with wider strides compared with individuals with transtibial amputation and controls (P < .0001). Individuals with amputation demonstrated more trunk kinematic variability in the presence of wider strides compared with individuals without amputation, and it appears that performing a concurrent cognitive task while walking did not change trunk or gait mechanics.

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