Type 2 diabetes mellitus (T2DM) is brought on by the dysfunction of beta cells within the endocrine pancreas, coupled with insulin resistance. This could possibly be induced by environmental or epigenetic aspects. A recent paper explains a model of diabetes that centers on the role of obesity in glucose dysregulation.

Study: Modeling the progression of Type 2 diabetes with underlying obesity. Image Credit: goffkein.pro/Shutterstock

Introduction

Mathematical models have been employed to predict the long-term effects of using anti-diabetic drugs at various stages of T2DM. Nevertheless, there isn’t any model to predict this condition considering the effect of multiple diabetogenic aspects, reminiscent of an environment that promotes obesity.

Available research indicates that hyperinsulinemia worsens insulin resistance and vice versa. Some scientists claim that beta cells turn into hyper-responsive to fat or glucose, producing abnormally high insulin levels. This causes insulin resistance as a protective mechanism to stop insulin-induced metabolic stress.

The model reported in the present paper, which appears in PLOS Computational Biology, analyzed diabetes progression regarding multiple diabetogenic aspects, including those related to the person’s obesity threshold for increased diabetes risk, those relating ethnicity to a tolerance of things promoting weight gain above the obesity threshold, in addition to the effect of bariatric surgery on T2DM risk.

What did the study show?

Based on the research gap, the scientists developed a model that examines the impact of high insulin levels on insulin resistance. It will investigate the results of multiple aspects linked to the event of diabetes by way of beta cell dysfunction.

This generalized model constructed by the scientists was then narrowed down by specifying an obesity-related diabetogenic factor. It examined how obesity affects glucose regulation within the body. It predicted changes in glucose and insulin levels over a human lifetime, showing how liver glucose production, rate of insulin release, and growth of functional beta cell mass modified when exposed to the obesity-related diabetogenic factor.

These long-term trends showed a detailed correlation to actual longitudinal data when fitted to a selected population, on this case, Pima Indian individuals. This group was chosen due to long follow-up data available on the long-term changes and direction of glucose concentrations.

The model could differentiate the hyperinsulinemic subject without blood glucose abnormality from those with prediabetes and overt diabetes. In an environment that highly promotes obesity, progression to hyperinsulinemia occurred in a mean of seven years. A decade later, diabetes set in.

In about twenty years, beta cell failure began to manifest as declining insulin levels, with actual insulin deficiency setting in with time.

The simulation also showed that when the identical individual was exposed to an environment with only a light obesogenic risk, the speed of progression and severity of disease were markedly reduced.

This supports the finding that weight reduction of obese patients helps alleviate diabetes.”

The outcomes confirmed what the scientists suspected. With proper control of obesity, T2DM could possibly be reversed or postponed, or not less than its severity reduced. This also explains the dramatic effect of the bariatric Roux-en-Y procedure that acts via reduced liver gluconeogenesis and reversal of beta cell dysfunction, to provide a rapid and sturdy restoration of euglycemia. The model could help determine the fitting time and patient for such surgeries to have the very best consequence.

Secondly, individual-specific differences in the extent of beta-cell dysfunction and insulin resistance were reflected within the variation in T2DM risk. So long as the obesity-related diabetogenic factor remained subthreshold, the person remained euglycemic though obese. As the edge was crossed to greater degrees, diabetes began to progress.

Such individualized threshold values, which give warning signs of obese levels for taking vital interventions to stop the commencement of diabetes, could also be beneficial for clinical decision making.”

An idea called personal fat threshold (PFT) is getting used to personalize food regimen plans for diabetic patients, using individualized susceptibilities to excessive lipids of specific types, in addition to the quantity of fat stored within the pancreas and liver.

Similarly, ethnic groups with basal hyperinsulinemia could successfully stave off diabetes by reducing exposure to obesogenic aspects.

Finally, the scientists checked out the biological mechanism of several key parameters laid out in this model and located much of relevance to the event of T2DM. Some interesting insights were obtained, including the expected improvement in prognosis when treatment was aimed toward minimizing the hostile effect of a diabetes risk factor on the beta cells, in comparison with improving the environment that promoted diabetes. That’s, beta cells controlled glucose levels higher when shielded from a hostile environment, relatively than when treatment efforts were focused on changing the environment through, as an example, dietary modifications or exercise.

Again, some patients showed poorer glucose control despite increased insulin sensitivity, indicating that insulin resistance just isn’t the one goal vital within the treatment of diabetes. Certain individuals develop severe diabetes rapidly after an extended period of euglycemia. This preceding prolonged period of fantastic glucose control was traceable to lower glucose production within the liver, indicating the importance of this as a therapeutic and preventive goal.

What are the implications?

This study may encourage precise interventions to stop diabetes and facilitate individualized patient treatment.”

Though used here to know how diabetes progresses in an obesogenic environment, the model can investigate the results of other aspects, reminiscent of thyroid hormone or epinephrine oversecretion on the glucose regulatory system within the body.