Increased orosomucoid in urine is an independent predictor of cardiovascular and all-cause mortality in patients with type 2 diabetes at 10 years of follow-up☆,☆☆,★,★★
Introduction
Patients with T1DM and T2DM have a higher mortality rate than the general population (Gall et al., 1995, Gu et al., 1998, Morrish et al., 1990). Recent data have suggested that the higher mortality rate among patients with diabetes may be declining, but it is still higher than the general population (Hansen et al., 2012, Monesi et al., 2012). The high mortality among patients with diabetes is—among other causes—due to a higher cardiovascular mortality (Gall et al., 1995, Gu et al., 1998, Morrish et al., 1990, Seshasai et al., 2011). The increased incidence of cardiovascular mortality in patients with diabetes is likely due to inflammatory processes involved in the pathophysiology of the disease (Kvasnicka et al., 1998, Pickup et al., 1997, Poland et al., 2001, Ross, 1993).
Orosomucoid, a glycoprotein that acts as an acute-phase reactant in inflammation, is found at elevated serum levels in patients with T2DM, compared to the serum levels in healthy individuals (Kvasnicka et al., 1998, Narita et al., 2004, Pickup et al., 1997). Pickup et al. (1997) found that serum s-orosomucoid levels were even higher in patients with both T2DM and metabolic syndrome, which indicates that adipose tissue plays an important role in the pathogenesis of increased s-orosomucoid.
The exact role of orosomucoid has not been established. In adipocytes in obese mice in response to metabolic changes and inflammation, orosomucoid acts as a modifier of inflammation by suppressing the interaction between adipocytes and macrophages (Lee et al., 2010).
Microalbuminuria is a well-known predictor of increased mortality in patients with diabetes and is systematically monitored to evaluate the renal function and general prognosis in these patients (Gall et al., 1995; Jarrett et al., 1984; Mogensen, 1984, Neil et al., 1993, Schmitz and Vaeth, 1988, Stephenson et al., 1995). Previous studies have shown that the urinary orosomucoid excretion rate (UOER) is elevated in patients with diabetes (Christiansen et al., 2002, Christiansen et al., 2005, Jiang et al., 2009). Reports have documented that UOER increased in parallel with urinary albumin excretion rate (UAER), but an increased UOER could be detected earlier when UAER was at a normal level (Christiansen et al., 2002, Christiansen et al., 2005, Jiang et al., 2009). Increased UOER was an independent predictor of diabetic nephropathy in patients with T1DM and T2DM (Jiang et al., 2009).
The data on which this study is based showed that an increase in UOER was a strong and independent predictor of cardiovascular and all-cause mortality in patients with T2DM at 2.4 years of follow-up (Christiansen et al., 2002). At 5 years of follow-up, increased UOER independently predicted cardiovascular mortality in the total cohort of patients with T2DM and in a subgroup of patients with T2DM with normal UAER; this observation indicates that UOER is an earlier marker of cardiovascular mortality than UAER (Christiansen et al., 2005). Furthermore, there was a significant correlation between UOER and mortality in patients with T1DM, although increased UOER was not an independent predictor of mortality in this group of patients.
The aim of the present study was to confirm whether increased UOER is an independent predictor of cardiovascular and all-cause mortality in patients with T2DM at 10 years of follow-up. Additionally, we aimed to evaluate whether increased UOER is independently predictive of mortality in patients with T1DM.
Section snippets
Subjects
We conducted this study based on data extracted from patients followed in the outpatient clinic at Amager Hospital, Copenhagen, from 1995 to 1998, including 430 patients with T2DM and 148 patients with T1DM. The cohort study consecutively included all patients who attended the outpatient clinic at Amager Hospital, Copenhagen with T2DM and T1DM and dipstick negative overnight urine samples. The following parameters at baseline were documented retrospectively from the patients' medical records:
Results
Table 1 shows baseline clinical data. In both T1DM and T2DM, patients with increased UOER had higher levels of p-creatinine and UAER and more patients were treated with ACE-I. In patients with T2DM, the group of patients with increased UOER were predominately men, were a little older and had been diagnosed with diabetes for a little longer. For further details, see previously published articles (Christiansen et al., 2002, Christiansen et al., 2005).
Discussion
Our results demonstrated a statistically significant higher mortality rate in patients with T1DM and T2DM with increased UOER at 10 years of follow-up.
In patients with T2DM, increased UOER was also associated with a higher mortality rate in the subgroup of patients with normal UAER. Increased UOER was an independent and strong predictor of mortality when adjusted for all available explanatory baseline factors in the total cohort and in the subgroup of patients with normal UAER. In the analysis
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Conflicts of interests: None.
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Ethics: The local ethics committee in Copenhagen approved the study protocols (H-3-2012-FSP4 and H-3-2012-FSP5).
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Grant support: None.
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Previous presentations: The abstract was presented, in part, at the annual meeting of the Danish Endocrine Society, Hotel Hvide Hus, Aalborg, Denmark, January 18, 2013, and the annual Science Day, Amager Hospital, Copenhagen, Denmark, March 21, 2013. The abstract has not been published.