Uses of fasting plasma glucose and HBA1C levels in the prediction of early developed type 2 diabetes mellitus in individuals with impaired fasting plasma glucose: A comparison to oral glucose tolerance test

The diagnosis of type 2 diabetes mellitus (T2DM) is currently based on results of fasting plasma glucose (FPG), HbA1C levels and/or oral glucose tolerance test (OGTT). About 11-30% of individuals with impaired fasting plasma glucose (IFG) have T2DM diagnosed by OGTT (1-3). Though OGTT has high sensitivity and specificity, it is however not as practical as using FPG and HbA1C levels in the diagnosis of T2DM. The objectives of this study were to examine the prevalence and determine cut-off levels of FPG and HbA1C that can most effectively predict the presence of early developed T2DM diagnosed by OGTT in individuals with IFG, and to study the pathophysiological characteristics in prediabetes and early developed T2DM. Standard 75-gram OGTT was performed in 117 subjects with IFG. Plasma glucose and insulin levels were measured every 30 minutes during OGTT. The insulin sensitivity and beta-cell function were calculated by using six formulas: 1) homeostatic model assessment (HOMA) β-cell function, 2) insulinogenic index, 3) Stumvoll first phase insulin secretion, 4) Stumvoll second phase insulin secretion, 5) HOMA-estimated insulin resistance (HOMA-IR), and 6) Matsuda index, using plasma glucose and insulin levels during OGTT. The results show that, in subjects with IFG, the prevalences of T2DM, prediabetes (IFG and/or impaired glucose tolerance test (IGT)), and normal glucose tolerance (NGT) diagnosed by OGTT criteria were 32.4%, 47.9%, and 19.7%, respectively. Receiver operating characteristic (ROC) curve analysis showed that the HbA1C level of 6.2% was the best cut-off value in the prediction of the presence of T2DM with a sensitivity of 44.7% (95% Cl = 28.6-61.7%), specificity 79.7% (95% CI = 69.2-88.0%), positive predictive value (PPV) 51.5%, and negative predictive value (NPV) 75.0%. The FPG value of 105 mg/dl was the best cut-off value in the prediction of the presence of T2DM with a sensitivity of 42.1% (95% Cl = 26.3-59.2%), specificity 81% (95% CI = 70.6-89.0%), PPV 51.6%, and NPV 74.4%. Subjects with T2DM and combined IFG and IGT had significantly lower HOMA-IR and higher Matsuda index than those with NGT (p <0.05). Subjects with T2DM had significantly lower insulinogenic index, and Stumvoll second phase insulin secretion compared to those with NGT (p <0.05). In conclusions, about one-third of individuals with IFG have early developed T2DM diagnosed by OGTT criteria. HbA1c is more useful glycemic parameter than FPG in the prediction of early developed T2DM. Individuals with HbA1C of ≥6.2% and/or FPG of ≥105 mg/dl should receive OGTT if available or closer monitoring of FPG and HbA1C levels. In combined IFG and IGT, decreased insulin sensitivity is the main pathophysiological defect. Whereas, in early developed T2DM, the main pathophysiological defects are decreased hepatic and peripheral tissue insulin sensitivity, in combination with impaired first and second phases of insulin secretion.