PROJECT SUMMARY/ABSTRACT
Rayhan A. Lal, MD is an Instructor in the Divisions of Adult and Pediatric Endocrinology at Stanford University.
As an electrical engineer and computer scientist with type 1 diabetes, his primary research interest is the
design, development and testing of new diabetes technologies. This K23 proposal will provide a structured
clinical research training experience with formal mentorship that will enable Dr. Lal to become an independent
clinical researcher with expertise in automated insulin delivery.
Subcutaneous “hybrid” closed-loop systems modulate insulin delivery based on continuous glucose data but
require users to announce meals. Despite promising randomized controlled trials, our published real-world
experience with the first commercial subcutaneous system shows that 46% of users presenting to clinic entirely
discontinue “Auto Mode” within 1 year. While some barriers may be overcome, the optimal technological
solution requires high user satisfaction and optimal glycemic control with minimal user intervention.
In this application, Dr. Lal proposes several studies to understand and optimize the intraperitoneal delivery of
insulin for a future autonomous implantable system. Intraperitoneal insulin delivery acts faster than
subcutaneous. The “tail” of insulin action is also shorter, making it easier to upregulate and downregulate
insulin levels with fewer time delays which is essential for automated insulin delivery. Intraperitoneal insulin
delivery also partially restores glucagon response to hypoglycemia and exercise, even in long-standing type 1
diabetes. The improved kinetics and safety from restored glucagon secretion make this system ideal for fully
automated insulin delivery. There is also a significant positive experience among users of implanted
intraperitoneal insulin therapy.
The specific aims of Dr. Lal’s study are to: (1) evaluate BMI, body composition, bone health and human factors
associated with intraperitoneal insulin among worldwide users, centered in Montpellier, and compare them to
matched controls with type 1 diabetes using subcutaneous insulin, (2) assess the speed and glucagon counter-
regulatory response to intraperitoneal faster acting insulin apart (Fiasp), and (3) use the available data to
perform in silico modeling and determine a control strategy that keeps glycemic control in range (70-180mg/dL)
over a variety of simulated conditions. His mentors include Drs. Buckingham, Maahs, Hood and Renard
worldwide leaders in diabetes technology.
In addition to coursework in epidemiology, statistics, study design, human protection and ethics, Dr. Lal will
also pursue a Biodesign faculty fellowship, offered at Stanford to promote the development of new health
technology. Dr. Lal’s long-term research objective is to collaborate with a diabetes device manufacturer,
PhysioLogic Devices (see letter of support from Peter Lord), to develop and test an implanted fully closed-loop
intraperitoneal insulin delivery system, optimizing time in range and eliminating the daily burdens of diabetes.