Prediabetes was defined as fasting plasma glucose (FPG) 100–125 mg/dl (IFG) or HbA1c 5.7–6.4% (IA1c). This study was approved by the Institutional Review Board of Samsung Seoul Hospital and carried out in accordance with the recommendations of the Declaration of Helsinki. Thus, the final number of participants in our study was 9,807 (4,628 men and 5,179 women). No subjects showed evidence of cancer or chronic infection in their electronic records. From the baseline data, which were collected when the participants first visited the hospital, 13,393 individuals were excluded for the following reasons ( S1 Fig): 1) baseline type 2 diabetes ( n = 1,321), prediabetes especially IFG or IA1c ( n = 4,736) or MetS ( n = 962) 2) history of cardiovascular disease including myocardial infarction or stroke ( n = 692) 3) new onset type 2 diabetes ( n = 28) and prediabetes ( n = 2,053) within one year of follow-up 4) diagnosis of type 2 diabetes prior to receiving an prediabetes diagnosis ( n = 23) 5) < 20 years old ( n = 4) 6) abnormal liver function ( n = 338), which was defined as either elevated levels of total bilirubin, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) that was more than twice the upper normal limit, or being positive for the hepatitis B surface antigen ( n = 955) or hepatitis C antibody ( n = 191) 7) estimated glomerular filtration rate (GFR) < 60 ml/min/1.73m 2, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula ( n = 180) 8) missing clinical variables ( n = 1,287) and 9) development of MetS prior to prediabetes onset ( n = 985). The health check-up programs included anthropometric data, laboratory data, and questionnaires about patient medical history and lifestyle.

In all, 24,185 adults underwent voluntary comprehensive health check-ups between January 2006 and December 2012 at Samsung Medical Center. We further examined the effect of serum albumin on the risk for progression to overt diabetes in prediabetic subjects. Herein, we sought to investigate whether baseline and change in serum albumin levels during an observation period could be independent risk factors for prediabetes especially impaired fasting glucose (IFG) or hemoglobin A1c (IA1c) in subjects without baseline and new MetS.

However, the association between serum albumin and glycemic alteration in subjects without evident insulin resistance has rarely been examined. Additionally, declines in insulin sensitivity had a greater effect on diabetes development than did insulin resistance, especially in Asian populations. In fact, one longitudinal study showed paradoxical contributions to incident MetS by baseline serum albumin concentration and changes in serum albumin. Previous studies that investigated associations between serum albumin and diabetes included subjects with MetS at baseline or incident MetS during the follow-up period, indicating that some portion of the included participants was already susceptible to developing type 2 diabetes, or that independent association between serum albumin and diabetes was partially interrupted by incident MetS before diabetes development. Serum albumin concentration was positively associated with prevalence of MetS, whereas increase in serum albumin over time might protect against MetS development. Low serum albumin concentration enhanced the risk for incident type 2 diabetes however, inverse correlations have been reported as well. Based on the potential antioxidant properties of serum albumin, emerging evidence indicates that serum albumin concentration might be associated with metabolic disorders such as type 2 diabetes and metabolic syndrome (MetS). Serum albumin is the most abundant plasma protein and it provides oncotic pressure, transports bilirubin and other hormones, and serves as an extracellular antioxidant agent.

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