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The most common form of diabetes, type 2 diabetes (T2D) is a failure of insulin-secreting pancreatic beta-cells to increase insulin to the level required to maintain normal blood glucose. Thus, identifying beta-cell function (BCF) and insulin sensitivity (SI) in those who are at high risk is crucial to preventing and delaying the disease. An oral glucose tolerance test (OGTT) is routinely used under clinical settings. Conventional metabolic parameters during OGTTs have been utilized in research fields and patient care. However, the parameters are calculated with algebraic formulae rather than the whole data profiles. Thus, we have developed a mathematical model and an algorithm to fie the model to OGTTs to estimate the metabolic parameters (Ha et al. AJP 2024, Ha and Sherman AJP 2020, Ha et al. Endocrinology 2016). Recently, we have extensively worked on clinical applications of the model-derived parameters to identify the most common pathways to T2D in Koreans. Specifically, we fitted a 10-year longitudinal data set of Korean Genome and Epidemiology Study (KoGES) (N=2683, age=50.5±7.7 years; BMI, 24.9±3.0 kg/m2, non-diabetes at baseline) to estimate mathematical model-derived insulin sensitivity and beta-cell function indices were used as metabolic surrogates. Then, a k-means clustering algorithm was applied to the indices to classify six metabolically distinct non-diabetes subgroups. The most common pathway in Korean is low beta-cell function at baseline and worsening insulin sensitivity over the course of the disease progression. Thus, we conclude that Koreans have limited ability to increase insulin secretion, so they are at risk for T2D with even a small drop in insulin sensitivity. |