Biology subjects

Mantzoros, C.

Publications and source records attributed to Mantzoros, C..

3 recordsLinked to original sources

bioRxiv2022

Patient-specific deep offline artificial pancreas for blood glucose regulation in type 1 diabetes

Due to insufficient insulin secretion, patients with type 1 diabetes mellitus (T1DM) are prone to blood glucose fluctuations ranging from hypoglycemia to hyperglycemia. While dangerous hypoglycemia may lead to coma immediately, chronic hyperglycemia increases patients risks for cardiorenal and vascular diseases in the long run. In principle, an artificial pancreas - a closed-loop insulin delivery system requiring patients manually input insulin dosage according to the upcoming meals - could supply exogenous insulin to control the glucose levels and hence reduce the risks from hyperglycemia. However, insulin overdosing in some type 1 diabetic patients, who are physically active, can lead to unexpected hypoglycemia beyond the control of common artificial pancreas. Therefore, it is important to take into account the glucose decrease due to physical exercise when designing the next-generation artificial pancreas. In this work, we develop a deep reinforcement learning algorithm using a T1DM dataset, containing data from wearable devices, to automate insulin dosing for patients with T1DM. In particular, we build patient-specific computational models using systems biology informed neural networks (SBINN), to mimic the glucose-insulin dynamics for a few patients from the dataset, by simultaneously considering patient-specific carbohydrate intake and physical exercise intensity.

systems biology↗

bioRxiv2021

Daily transient coating of the intestine leads to weight loss and improved glucose tolerance

The worsening obesity epidemic has driven a parallel increase in incidence of type-2 diabetes (T2D) found in 13% of the adult US population. Roux-en-Y gastric bypass surgery (RYGB) is the golden standard surgical treatment for obesity-related T2D. However, over 70% of T2D patient do not meet the NIH criteria for surgery, and many that do, are reluctant to consider such an invasive intervention. Mechanisms behind the antidiabetic effect of RYGB are not clearly understood, but isolation of proximal bowel from nutrient exposure plays a critical role. In this study, we tested the impact of daily administration of an oral gut coating agent, LuCI (Luminal Coating of the Intestine), in controlling weight and insulin resistance. LuCI is not systemically absorbed and provides a transient coating of the proximal intestines and excludes the coated bowel from nutrient contact, thus mimicking the effects of RYGB. We demonstrate that LuCI results in weight loss and improved insulin sensitivity in a rat DIO model. LuCI also appears to replicate hormonal changes seen after RYGB, by increasing post-prandial GLP-1 and GIP levels. LuCI has the potential to replicate the metabolic benefit of surgery and be a novel therapeutic strategy for obesity associated T2D.

bioengineering↗

bioRxiv2018

Quantifying platelet margination in diabetic blood flow

Patients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities strongly associated with cardiovascular diseases. In addition to the changes of numerous coagulation factors such as elevated levels of thrombin and fibrinogen, the abnormal rheological effects of red blood cells (RBCs) and platelets flowing in blood are crucial in platelet adhesion and thrombus formation in T2DM. An important process contributing to the latter is the platelet margination. We employ the dissipative particle dynamics method to seamlessly model cells, plasma, and vessel walls. We perform a systematic study on the RBC and platelet transport in cylindrical vessels by considering different cell shapes, sizes and RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and hematocrit. In particular, we use cellular-level RBC and platelet models with parameters derived from patient-specific data and present a sensitivity study. We find T2DM RBCs, which are less deformable compared to normal RBCs, lower the transport of platelets toward the vessel walls whereas platelets with higher mean volume (often observed in T2DM) lead to enhanced margination. Furthermore, increasing the flowrate or hematocrit enhances platelet margination. We also investigated the effect of platelet shape and observed a non-monotonic variation with the highest near-wall concentration corresponding to platelets with moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs), whose count is increased notably in T2DM patients. We find that WBC rolling or WBC adhesion tend to decrease platelet margination due to hydrodynamic effects. To the best of our knowledge, such simulations of blood including all blood cells have not been performed before, and our quantitative findings can help separate the effects of hydrodynamic interactions from adhesive interactions, and potentially shed light on the associated pathological processes in T2DM such as increased inflammatory response, platelet activation and adhesion, and ultimately thrombus formation.

biophysics↗