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Higher osteoprotegerin levels associated with foot ulcer in type 1 diabetes
In patients with type 1 diabetes, higher levels of the glycoprotein osteoprotegerin are associated with development of a foot ulcer, independent of other well-known risk factors, according to recent findings.
“Diabetic foot ulcers are a frequent, disabling and costly occurrence; however, it is a complication often overlooked in terms of research,” Emilie Hein Zobel, MD, of the Steno Diabetes Center in Gentofte, Denmark, and colleagues wrote. “To the best of our knowledge, we are the first to show an association between higher levels of [osteoprotegerin] and development of foot ulcer in type 1 diabetes, independent of other risk factors. This might be attributed to the role of [osteoprotegerin] both in peripheral vascular disease and neuropathy; the two major factors contributing to foot ulcer.”
In a prospective cohort study, Zobel and colleagues analyzed data from 573 adults with longstanding type 1 diabetes and persistent normoalbuminuria (n = 176) or type 1 diabetes and diabetic nephropathy (n = 397), recruited from the Steno Diabetes Center between 1993 and 2002. Participants provided blood samples; researchers measured serum cholesterol, HbA1c, urinary albumin excretion rate, serum creatinine level and estimated glomerular filtration rate. Researchers assessed participants for the presence of foot ulcer, Charcot foot, amputation, foot pulse and claudication at baseline and from patient record information; baseline information on lower limb vascular surgery was not available. Peripheral sensory neuropathy was evaluated at baseline and follow-up.
Participants with foot complications were excluded when analyzing the association between osteoprotegerin and development of foot complications. At baseline, 23 participants had a foot ulcer; three had Charcot foot; 14 had a lower limb amputation or vascular surgery; 31 had absent foot pulse and 198 had neuropathy. Of the remaining patients, 153 developed foot ulcer; 14 developed Charcot foot; 53 underwent amputation or vascular surgery during median follow-up time of 12.7 years.
In models adjusted for age, sex, nephropathy status, smoking status, HbA1c, systolic blood pressure, serum cholesterol, high sensitivity C-reactive protein, eGFR and presence of neuropathy or claudication at baseline, researchers found that higher osteoprotegerin level was associated with development of foot ulcer (HR = 1.75; 95% CI, 1.04-2.97). Other independent risk factors for development of foot ulcer included neuropathy at baseline (HR = 1.98; 95% CI, 1.17-3.37); nephropathy (HR = 2.05; 95% CI, 1.14-3.7) and male sex (HR = 1.36; 95% CI, 1.59-1.01).
Researchers also found that higher osteoprotegerin was associated with development of a combined endpoint of Charcot foot, amputation, vascular surgery and foot ulcer after adjustment for age and sex (P = .001), but any association was lost after adjustment for other factors.
“Measuring [osteoprotegerin] is relatively uncomplicated and inexpensive,” the researchers wrote. “Our findings, and previous studies, illustrate that this biomarker may also be helpful in the risk assessment for foot complications, and in particular for foot ulcers in type 1 diabetic persons. However, our findings need to be validated and further studies are needed to establish cutoff values and to document the added value to currently available strategies before using [osteoprotegerin] in screening.” – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
AUTHORS:
Zobel EH, von Scholten BJ, Lajer M, Jorsal A, Tarnow L, Rasmussen LM, Holstein P,
Parving HH, Hansen TW, Rossing P.
BACKGROUND:
The bone-related peptide osteoprotegerin has been linked to vascular calcification and peripheral vascular disease. We investigated the association between osteoprotegerin and development of foot complications in persons with type 1 diabetes. ...