Adipocytokine zinc α2 glycoprotein (ZAG) as a novel urinary biomarker for normo-albuminuric diabetic nephropathy.

OBJECTIVE: A substantial proportion of diabetic nephropathy individuals are non-albuminuric. Using a proteomic approach, we searched for novel urinary biomarkers. METHODS: We studied three groups (n = 6 per group) of males with Type 2 diabetes: (1) normal renal function; (2) classical diabetic nephropathy (urinary albumin-creatinine ratio > 1000 mg/g and glomerular filtration rate < 60 ml/min.1.73 m(2) ) and (3) non-albuminuric diabetic nephropathy (glomerular filtration rate < 60 ml/min.1.73 m(2) and urinary albumin-creatinine ratio < 30 mg/g). We used two-dimensional fluorescence differential gel electrophoresis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide identification and western blot validation in the study. RESULTS: Sixty protein spots were differentially abundant between the non-albuminuric and macro-albuminuric subjects (> 2.5-fold, P < 0.05). In the non-albuminuric subjects, in addition to previously reported α(1) -microglobulin, the next most interesting spot (upregulated 3.44-fold, P = 0.0026) was human zinc-α(2) -glycoprotein, a novel adipose-cytokine associated with glomerular injury. This was confirmed by western blot and replicated in female diabetic nephropathy subjects. CONCLUSIONS: From our preliminary results, human zinc-α(2) -glycoprotein may be a novel urinary biomarker for non-albuminuric diabetic nephropathy.

Elevated undercarboxylated and reduced carboxylated osteocalcin are associated with metabolic syndrome in middle age Asian females.

Accumulating data suggest that bone plays a role in energy metabolism through decarboxylation of osteocalcin. Thus, we aimed to study the association of circulating under--carboxylated osteocalcin (UC-OCN) and car-boxylated osteocalcin (C-OCN) with metabolic syndrome in middle aged Asian population.In this cross-sectional study, 131 middle aged Asian subjects were recruited. Circulating UC-OCN, C-OCN and parameters of metabolic phenotype were measured.Circulating UC-OCN was increased in subjects with metabolic syndrome (8.1±7.2 ng/ml vs. 5.9±4.6 ng/ml, p=0.036). In contrast, C-OCN showed a non-significant trend towards reduction in subjects with metabolic syndrome (3.6±2.2 ng/ml vs. 4.3±1.8 ng/ml, p=0.057). Further analysis revealed that changes in both UC-OCN and C-OCN occurred primarily among females with metabolic syndrome. Interestingly, neither forms of OCN differed significantly between individuals with and without metabolic syndrome in males. Logistic regression revealed that UC-OCN was independently associated with metabolic syndrome after adjusting for multiple covariates. However, association between metabolic syndrome and C-OCN was dependent on gender (i. e., amongst females only) in the fully adjusted regression model.Variation in OCN (including its sub-species) was associated with variation in metabolic parameters amongst Asian adults. Circulating UC-OCN was increased while C-OCN was decreased in treatment-naïve females with metabolic syndrome. Our preliminary observations further supported a potential link between bone and energy metabolism in humans.