Early-Phase Changes in Serum Free Fatty Acid Levels After Glucose Intake Are Associated With Type 2 Diabetes Incidence: The Hiroshima Study on Glucose Metabolism and Cardiovascular Diseases

Abstract

OBJECTIVE Experimental studies suggest that excess serum free fatty acid (FFA) levels result in impaired glucose metabolism. This study investigated the relationship between changes in serum FFA levels after glucose intake and type 2 diabetes risk. RESEARCH DESIGN AND METHODS This observational study included 6,800 individuals without diabetes who underwent a 75-g oral glucose tolerance test. Serum FFA levels were measured before and 30 and 60 min after glucose intake. The percentages of changes in serum FFA levels from 0 to 30 and from 30 to 60 min were compared, and a low rate of change in FFA levels was determined using the receiver operating characteristic curve analysis. RESULTS Over a mean 5.3-year follow-up period, 485 participants developed type 2 diabetes. After adjusting for plasma glucose levels and indices of insulin resistance and β-cell function, low rates of change in FFA levels at 0–30 min (adjusted odds ratio [aOR] 1.91; 95% CI 1.54–2.37) and 30–60 min (aOR 1.48; 95% CI 1.15–1.90) were associated with the incidence of type 2 diabetes. Stratified analysis revealed that the low rate of change in FFA levels at 30–60 min (aOR 1.97; 95% CI 1.05–3.69) was associated with the incidence of type 2 diabetes even in participants with normal fasting glucose levels or glucose tolerance. CONCLUSIONS Changes in serum FFA levels within the 1st h after glucose intake could be a primary predictor of type 2 diabetes. This change may occur prior to the onset of impaired glucose metabolism.