Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

B-chain with a phenylboronic acid (PBA), a chemical group

known to bind to glucose. Lead candidates were further

evaluated in mouse models of diabetes. This approach has

several advantages over previous approaches to develop GRI.

First, the binding between PBA and glucose has a fast binding

profile, which is needed for fast responses to elevated blood

glucose. Second, PBA-containing insulin analogs could achieve

glucose-responsive behaviors without the injection of foreign

biomaterials and their associated risk of immunogenicity.

Furthermore, the circulating insulin analogs could be inacti-

vated at low blood glucose levels, which reduce the risks of

hypoglycemia. This promising strategy may lead to major

breakthroughs and represents a truly novel paradigm shift in

the treatment of diabetes.

Closed-Loop System and CGM

S33-1

The use of closed loop in outpatient/home studies

Roman HOVORKA

Institute of Metabolic Science and Department

of Paediatrics, University of Cambridge, Cambridge, UK

Type 1 diabetes is one of the most common endocrine

problems in childhood and adolescence persisting into

adulthood and remains a serious chronic disorder with

increased morbidity, mortality and reduced quality of life.

Research over past decades showed that good blood glucose

control dramatically lowers the risk of serious diabetes

complications. Yet, studies reveals that even the best con-

trolled patients spend less than 50 percent of their day

within the normal blood glucose range, especially overnight,

when patients are most vulnerable to episodes of low glucose

levels.

Continuous glucose monitoring devices and insulin pumps

can be combined to form a closed loop apparatus, also known

as the Artificial Pancreas, an emerging medical device which

may transform management of type 1 diabetes. This promis-

ing approach differs from conventional insulin pump therapy

through the use of a control algorithm which directs sub-

cutaneous insulin delivery according to sensor glucose levels.

Closed-loop prototypes have been tested extensively under

controlled laboratory conditions in youth, adults and in

pregnancy demonstrating reduced risk hypoglycaemia and

increased time in target glucose range. Pioneering transitional

and home studies have been performed to demonstrate

benefits in target settings. Exercise and meal consumption

present particular challenges owning to rapid changes in

glucose excursions and may require user involvement, co-

administration of hormone counteracting insulin action or

faster insulin analogues. Focused academia-industry collab-

oration is required to exploit closed-loop technologies, to

bridge gaps, and to accelerate transition to clinical practice.

Scalability, low biological risk and innovation potential are the

main appeal.

S33-2

Redefining diabetes management by technology in children

with diabetes: from insulin pumps and continuous glucose

monitors to the artificial pancreas system

Eda CENGIZ

Pediatric Endocrinology and Diabetes, Yale School of

Medicine, New Haven, CT, USA

The incorporation of new technology into diabetes treatment

provided diabetologists with additional tools such as glucose

sensors, smart insulin pumps, and the promise of closed

loop insulin therapy (a.k.a the artificial pancreas project), a

mechanical solution for diabetes management to restore

near-physiologic glycemic control automatically. Such a

system consists of three main elements: insulin delivery,

continuous glucose sensing, and a controller or algorithm

that, similar to the beta cell, regulates the proper amount of

insulin delivery at the proper time. The continuous glucose

monitor (CGM) technology allowed real time glucose mon-

itoring, detection of patterns and determination of rapid drop

or rise in glucose levels with continuous stream of data. The

integration of the CGM in to the insulin pump therapy

introduced the sensor augmented pump therapy (SAP). While

the benefit of CGM and SAP use to lower HbA1c levels has

been clearly shown in adults with diabetes, it has been

challenging to achieve the same success with children and

adolescents. This talk will provide finer details of the CGM

technology and summarize results of the key studies regard-

ing CGM and SAP use in children and adolescents with

diabetes. We will discuss unique limitations of CGM and SAP

use in the pediatric population and potential solutions to

overcome these challenges. The CGM and SAP technology of

the near future with new models that are in the pipeline and

new developments in the artificial pancreas system research

will be presented.

Obesity and Diabetes

S13-1

Roles for adipose ceramides in metabolic homeostasis

S.A. SUMMERS

Department of Nutrition and Integrative

Physiology, University of Utah, Salt Lake City, UT, USA

Adipocytes package incoming fatty acids into triglycerides and

other glycerolipids, with only a fraction spilling into a parallel

biosynthetic pathway that produces sphingolipids. During

obesity, the excessive entry of lipid into this pathway leads

to the aberrant accumulation of biosynthetic intermediates

such as ceramides that impair tissue metabolism and

function. Notably, genetic or pharmacological inhibition of

enzymes that drive ceramide synthesis (e.g. serine palmitoyl-

transferase, dihydroceramides desaturase, etc.) in mice ame-

liorates virtually all complications of obesity including insulin

resistance, steatosis, diabetes, hypertension, cardiomyopathy,

and atherosclerosis. To dissect the tissue-specific roles for

ceramides in nutrient homeostasis, we have produced mice

lacking serine palmitoyltransferase, the rate-limiting enzyme

in the ceramide biosynthesis cascade, in various body locales.

Using these mice, we determined that newly-synthesized

adipocyte sphingolipids drive profound changes in the adi-

pose phenotype to influence whole-body energy expenditure

and nutrient metabolism.

S13-2

Roles of G6PD in ROS and inflammatory responses of obese

adipose tissue

Sung Sik CHOE

, Mira HAM

, Kyung Cheul SHIN

, Goun CHOI

Jae Bum KIM

Department of Biological Sciences, Institute of

Molecular Biology and Genetics, National Creative Research

Initiatives Center for Adipose Tissue Remodeling, Seoul National

University, Seoul, Korea

Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting

enzyme of the pentose phosphate pathway, plays important

roles in redox regulation along with

de novo

lipogenesis.

Recently, it has been demonstrated that abnormal increase

of G6PD in obese adipose tissue mediates insulin resistance

due to imbalanced energy metabolism and oxidative stress.

However, it remains elusive whether the G6PD deficiency

in vivo

may relieve obesity-induced insulin resistance. In this

study, we have shown that hematopoietic G6PD defect alle-

viates insulin resistance in obesity, accompanied with reduced

adipose tissue inflammation. Compared to WT littermates,

G6PD-deficient mutant (G6PD

mut

) mice were glucose tolerant

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