Diabetes Mathematical Models
Diabetes mathematical models from our lab are listed below. The models illustrate how diabetes results from the interaction of insulin resistance and impairment of the ability of beta-cells to compensate for it.
This model for the pathogenesis of type 2 diabetes shows that disease onset is a threshold-crossing process, which explains why prevention is easier than cure. One of the predictions of the model is confirmed in the companion experimental paper.
- Chronic glucose exposure systematically shifts the oscillatory threshold of mouse islets: Experimental evidence for an early intrinsic mechanism of compensation for hyperglycemia.
- Glynn E, Ha J, Kennedy RT, Lu S, Satin LS, Sherman A, Thompson B, Vadrevu S.
- Endocrinology. (2016) 157(2):611-623. Abstract/Full Text
- Mathematical Model of the Pathogenesis, Prevention and Reversal of Type 2 Diabetes.
- Ha J, Satin LS, Sherman AS.
- Endocrinology. (2016) 157(2):624-635. Abstract/Full Text
This model accounts for the diversity of pathways typically followed, focusing on two extreme alternatives, one that goes through impaired fasting glucose (IFG) first and one that goes through impaired glucose tolerance (IGT) first. IFG generally results from primarily hepatic insulin resistance, while IGT results primarily from peripheral insulin resistance. We consider whether hyperinsulinemia may be a cause of insulin resistance rather than a consequence and find that this is at best a small effect.
- Type 2 Diabetes: One Disease, Many Pathways.
- Ha J, Sherman A.
- Endocrinol. and Metab. (2020) 319(2):E410-E426. Abstract/Full Text
Assessing Insulin Resistance
The Bergman-Cobelli Minimal Model is widely used to assess insulin resistance using data from an intravenous glucose tolerance test. Of particular interest to us are studies using this method to show that African Americans (AA) have greater insulin resistance than White Americans, a possible explanation for the greater risk of type 2 diabetes in AA. We have found, however, that the Minimal Model can be fooled in some cases into reporting greater insulin resistance when insulin secretion is during the test is greater. We show how additional data from oral glucose tolerance tests can be used to check if this is the case.
- When MINMOD Artifactually Interprets Strong Insulin Secretion as Weak Insulin Action.
- Ha J, Muniyappa R, Sherman AS, Quon MJ.
- Front. Physiol. (2021) 12:601894. Abstract/Full Text