A Glucose-Only Model to Extract Physiological Information from Postprandial Glucose Profiles in Subjects with Normal Glucose Tolerance

Abstract

Background: Current mathematical models of postprandial glucose metabolism in people with normal and impaired glucose tolerance rely on insulin measurements and are therefore not applicable in clinical practice. This research aims to develop a model that only requires glucose data for parameter estimation while also providing useful information on insulin sensitivity, insulin dynamics and the meal-related glucose appearance (GA). Methods: The proposed glucose-only model (GOM) is based on the oral minimal model (OMM) of glucose dynamics and substitutes the insulin dynamics with a novel function dependant on glucose levels and GA. A Bayesian method and glucose data from 22 subjects with normal glucose tolerance are utilised for parameter estimation. To validate the results of the GOM, a comparison to the results of the OMM, obtained by using glucose and insulin data from the same subjects is carried out. Results: The proposed GOM describes the glucose dynamics with comparable precision to the OMM with an RMSE of 5.1 ± 2.3 mg/dL and 5.3 ± 2.4 mg/dL, respectively and contains a parameter that is significantly correlated to the insulin sensitivity estimated by the OMM ( r = 0.7) Furthermore, the dynamic properties of the time profiles of GA and insulin dynamics inferred by the GOM show high similarity to the corresponding results of the OMM. Conclusions: The proposed GOM can be used to extract useful physiological information on glucose metabolism in subjects with normal glucose tolerance. The model can be further developed for clinical applications to patients with impaired glucose tolerance under the use of continuous glucose monitoring data.

Postprandial Plasma Glucose Measured from Blood Taken between 4 and 7.9 h Is Positively Associated with Mortality from Hypertension and Cardiovascular Disease

“…However, the use of PPG measured from blood taken between 3 and 7.9 h is inferior to PPG 4-7.9h , as PPG measured from blood taken between 3 and 3.9 h did not return to the baseline level and it was higher than PPG 4-7.9h [10]. In addition, PPG returned to baseline four hours after a meal regardless of meal type and mealtime [11]. Moreover, the current study confirmed that hourly PPG 4-7.9h was similar across the duration from 4 to 7.9 h. Therefore, it is necessary to investigate the association between PPG 4-7.9h and CVD mortality.…”

“…However, those studies did not investigate CVD mortality. In addition, measuring glucose at 1 or 2 h after a meal may not be ideal, as variation in diet could change PPG by more than 20 mg/dL [11], and variation in blood collection time (±0.5 h in practice [40]) could introduce bias as PPG is time sensitive around 1 to 2 h [11]. In contrast, the current study showed that PPG 4-7.9h was stable and hourly PPG 4-7.9h was comparable.…”

“…However, the PPG measured from blood taken between 3 and 3.9 h did not return to the baseline level and it was higher than PPG 4-7.9h [10]. A recent study showed that PPG returned to baseline four hours after a meal regardless of meal type (normal or high carbohydrate) and mealtime (breakfast, lunch, and dinner) [11]. Therefore, the use of PPG measured from blood taken between 3 and 7.9 h is inferior to PPG 4-7.9h and the association between PPG 4-7.9h and CVD mortality needs to be investigated.…”

Postprandial Plasma Glucose and Associated Cancer Mortality

“…12 That study has some limitations. First, measuring glucose at 2 h after a meal may not be ideal, as variation in diet 2 could change PPG by more than 20 mg/dL, 13 and variation in blood collection time (2 ± 0.5 h in practice 12 ) could introduce bias as PPG could be time-sensitive around 2 h. 13 Second, the use of antidiabetic medications could produce bias, as these medications affect PPG.…”

Methods for estimating insulin resistance from untargeted metabolomics data

“…HOMA-IR is relatively inexpensive since it is derived from measurement of glucose and insulin in a fasting blood sample. Despite its convenience, HOMA-IR is widely regarded to have significant limitations (Pisprasert et al 2013 ; Wallace et al 2004 ; Thompson et al 2014 ) and can even lead to different conclusions compared to other insulin resistance measures (Reaven 2013 ). Broadly speaking, it is widely accepted that methods such as the hyperinsulinemic-euglycemic clamp (Defronzo 1979 ) or the frequently sampled intravenous glucose tolerance test [FSIGT; (Bergman 1989 )] are more desirable.…”