Non-linear modelling of fasting plasma glucose Concentration and peak 2-hour insulin response to a glucose challenge in Australian Aboriginal People

Background - The aim of this study was to investigate the relationship between 2-hour insulin concentration and fasting plasma glucose concentration (FPG) in a population-based sample of Indigenous Australians.

Methods - Data collected from 2930 adults with unknown diabetic status were analyzed using three non-linear modeling methods: locally weighted regression (LOESS), generalized additive models (GAM), and fractional polynomial (fracpoly) regression procedures.

Results - Log fasting insulin and log 2-hour insulin had nonlinear relationships with FPG. All models indicated a consistent fit for 2-hour insulin response across FPG values of 3.5 135.8 mmol/l. GAM and fracpoly regressions overlapped across FPG values of 3.5 1313 mmol/l. The LOESS model had a slightly different pattern from FPG of 5.8-17 mmol/l. For all models, log 2-hour insulin concentration increased across FPG values from 3.5 137.0 mmol/l and decreased for FPG >7.0 mmol/l.

Conclusions - The 7.0 mmol/l FPG diagnostic cut-off represents the start of a diminishing second-phase insulin response to glucose, indicating that pancreatic output begins to decline at this FPG level. These results provide strong physiological rationale, beyond rising rates of clinical complications, for the revised fasting glucose diagnostic criterion of 7.0 mmol/l. Further research is needed to evaluate whether similar relationships exist for other high- and low-risk populations.