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Amputation abstract
Metabolic syndrome abstract
Benefits of long-term fenofibrate therapy on amputations in type 2 diabetes mellitus in the
FIELD trial
Author Block:
P. Colman, K. Rajamani, L.-P. Li, M. D'Emden, M. Voysey, A. Keech;
on behalf of the FIELD study investigators, c/o NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
Abstract:
Background and aims:
In the FIELD trial in 9795 patients with type 2 diabetes mellitus, fenofibrate reduced total cardiovascular events and retinopathy requiring laser therapy, suggesting effects on both macrovascular and microvascular complications. The study provided an opportunity to explore in detail the nature and predictors of amputations, which were also significantly reduced by treatment.
Materials and methods:
All on-study non-traumatic amputations were reviewed in blinded fashion by 2 clinicians. Amputations of digits and forefoot were classified as having a presumed microvascular basis provided that no prior or concurrent large vessel disease (including angioplasty and bypass surgery) in that same limb, or evidence of causative embolism, was present. Larger amputations or those with evidence of embolism or existing vascular disease in the affected limb were classified as macrovascular or mixed. All analyses of the effects of treatment were by intention-to-treat.
Results:
Compared with patients suffering any other cardiovascular event or no event during 5 years of follow-up, those with an amputation had a significantly longer duration of diabetes, higher systolic blood pressure, more current smoking, more prior vascular disease, more male gender, more microvascular disease and more baseline insulin use (all p<0.0001). Compared with subjects classified as having a macrovascular amputation, those with presumed microvascular amputations were slightly younger (p=0.03), heavier (p<0.001), had slightly higher HbA1c (p=0.07) and with more other microvascular disease at baseline, including known retinopathy, peripheral neuropathy and albuminuria (p=0.002).
Effects of fenofibrate on amputations |
|||
|
Relative risk reduction |
95% confidence interval |
p value |
Microvascular amputations |
47% |
8-70% |
0.025 |
Macrovascular amputations |
23% |
-21-51% |
0.26 |
All first amputations |
38% |
10-57% |
0.011 |
Conclusion:
Compared with amputations associated with large vessel limb disease, small digit (presumed microvascular) amputations occur in a population with higher levels of established microvascular complications of diabetes. The measured effects of fenofibrate on amputations were particularly striking in this group, further supporting important clinical benefits with fenofibrate treatment on microvascular disease in type 2 diabetes mellitus.