Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes

Abstract

Patients with Type II (non-insulin-dependent) diabetes mellitus have an increased risk of cardiovascular and all-cause mortality compared to the background population [1,2]. Microalbuminuria is a well-known predictor of increased mortality in patients with Type II diabetes [2±6]. The excess mortality is mainly caused by cardiovascular diseases [1,2,6].Orosomucoid is a glycoprotein (41 000 M r , content of carbohydrate 42 %) with a low isoelectric point of 2.7 [7]. Orosomucoid is synthesized in the liver and its serum concentrations are raised in conditions of inflammation and tissue repair [8]. The specific function of the protein is not known. In renal physiological investigations orosomucoid has been classified as a marker of increased glomerular permeability [9]. Diabetologia (2002) Abstract Aims/hypothesis. Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes.Methods. In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. Results. We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00±6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31±73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA 1 c , plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. Conclusion/interpretation. We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors. [Diabetologia (2002)

Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow-up

“…We also confirmed our previous observation that increased UOER is an independent predictor of cardiovascular mortality in patients with type 2 diabetes and micro-and macroalbuminuria at 2.4 years of follow-up [5]. Increased UOER, therefore, seems a superior marker for cardiovascular mortality compared with microalbuminuria in patients with type 2 diabetes.…”

“…Medical history was obtained from medical records. The registration of clinical parameters is described in detail elsewhere [5]. We registered the presence or absence of cardiovascular diseases (hypertension, coronary heart disease, previous myocardial infarction, stroke and congestive heart failure), diabetic retinopathy, smoking habits and medication (use of insulin and ACE inhibitors).…”

“…Blood and urine analyses Analyses of blood and urine are described in detail elsewhere [5]. Data on HbA 1 c and plasma creatinine were collected from routine blood analyses performed on fresh samples within a period of maximum 6 months before or after the corresponding urine sample.…”

“…Urinary orosomucoid excretion rate (UOER) was demonstrated to predict all-cause and cardiovascular mortality independently of classic risk factors in a 2.4-year followup study of patients with type 2 diabetes including patients with normo-, micro-and macroalbuminuria [5]. The study was not powered to show predictive value of UOER in the subgroup of patients with normal urinary albumin excretion rate (UAER); but still increased UOER was strongly associated with cardiovascular mortality in the normoalbuminuric subgroup.…”

“…The study was not powered to show predictive value of UOER in the subgroup of patients with normal urinary albumin excretion rate (UAER); but still increased UOER was strongly associated with cardiovascular mortality in the normoalbuminuric subgroup. Another limitation of the study was the lack of access to serum values of orosomucoid [5].…”