2016PATHWAY TO STOP DIABETES®

Pathway to Stop Diabetes®

The Pathway to Stop Diabetes initiative of the American Diabetes Association® is a transformational approach that is creating and supporting a new generation of exceptional diabetes researchers.

1

The prestigious, nomination-only Pathway awards attract and cultivate brilliant scientists at the peak of their creativity and accelerate research progress by providing substantial and sustained unrestricted funding; guiding the researchers with scientific and career mentoring; and creating systems and programs for collaboration, communication, and career advancement.

Three Pathway grant types support early-career investigators and those established in other fields:

• Pathway Initiator—For scientists currently in training through their transition to independence in diabetes research careers

• Pathway Accelerator—For diabetes researchers early in their independent careers

• Pathway Visionary—For scientists established in another field to apply their expertise and novel approaches to diabetes research for the first time

More than $40 million in generous gifts from individuals, foundations, and corporations, including Pathway corporate sponsors Novo Nordisk, Sanofi, AstraZeneca, the Eli Lilly and Company Foundation, and Merck, have allowed the Association to select and fund 23 stellar scientists who are already accelerating progress in diabetes research.

“It’s been an honor for Lilly Diabetes to be part of the support for Pathway’s program. Having Pathway awards and Pathway awardees is critical if we are to continue in our efforts to improve outcomes for people with diabetes.”

– David Kendall, MD, Vice President Medical, Lilly Diabetes

2

The Pathway PortfolioThe Pathway initiative supports a strong and balanced research portfolio, representing the full breadth of diabetes-related research topics.

2017 Pathway Initiator awardee Jonathan N. Flak, PhD, in the laboratory

Diabetes Type l Obesity

l Type 1 Diabetes

l Both Type 1 and Type 2

l Type 2 Diabetes

l Gestational Diabetes

l Prediabetes

Research TypeBasic Science l

Clinical and Translational Science l

Award Typel Initiator

l Accelerator

l Visionary

Awardee DegreePhD l

MD l

MD/PhD l

13%

17%

35%

22%

9%4%

74%

26%

44%

26% 30%

17%

66%17%

4

The Pathway Scientists

Jonathan N. Flak, PhDUniversity of Michigan

Stephen C.J. Parker, PhDUniversity of Michigan

Daniel J. Ceradini, MD, FACSNew York University

Zhen Gu, PhDNorth Carolina State University and University of North Carolina

Mayland Chang, PhDUniversity of Notre Dame

Marie-France Hivert, MDHarvard Medical School

Paul Cohen, MD, PhDThe Rockefeller University

Zachary A. Knight, PhDUniversity of California,San Francisco

Thomas Delong, PhDUniversity of Colorado, Denver

Aleksandar D. Kostic, PhDJoslin Diabetes Center

Michael D. Dennis, PhDPennsylvania State University, Hershey

Kathleen A. Page, MDUniversity of SouthernCalifornia

5

David A. Spiegel, MD, PhDYale University

Sumita Pennathur, PhDUniversity of California, Santa Barbara

Stephanie Stanford, PhDUniversity of California, San Diego

Wolfgang Peti, PhDUniversity of Arizona

Sarah A. Stanley, MD, PhDMount Sinai Health System

Celine E. Riera, PhDCedars-Sinai Medical Center

Joshua P. Thaler, MD, PhDUniversity of Washington

Andrew Scharenberg, MDSeattle Children’s Hospital

Sui Wang, PhDStanford University

Praveen Sethupathy, PhDUniversity of North Carolina

Phillip J. White, PhDDuke University

6

378research projects supported in 2016

351 150

Pathway Progress Through 2016Cumulatively, the Pathway program has supported 23 investigators who are making substantial progress and achieving key program objectives.

23Pathway scientists selected from

individuals, nominated as their institution’s single best candidate

> 400

>$40MRaised from corporate sponsors and

individual philanthropists to support Pathway

6New Pathway awardees

were selected from

106 nominees to start funding in

20175Pathway Initiator

awardees have secured their first independent faculty positions

7

38+Peer-reviewed publications

authored by Pathway awardees through 2016

378research projects supported in 2016

365

24/7

>$40MRaised from corporate sponsors and

individual philanthropists to support Pathway

3Patents filed by Pathway scientists to protect intellectual property and translate discoveries into diabetes tools and cures

8

Key Accomplishmentsof Pathway Scientists in 2016The 17 Pathway awardees who were funded during the 2016 calendar year made substantial progress in understanding the causes of diabetes and its complications.

Desmond A. Schatz, MD, the American Diabetes Association’s President, Medicine & Science, welcomes attendees to the 2016 Pathway Symposium in New Orleans.

TYPE 1 DIABETES Pathway Scientist Thomas Delong, PhD, has discovered a potential trigger for the autoimmune attack that causes type 1 diabetes. Delong et al. Science. 2016 Feb 12; 351(6274): 676-8.

TYPE 2 DIABETES Pathway Scientist Stephen Parker, PhD, has identified links between genetics and environmental factors that influence type 2 diabetes risk.Scott et al. Nat. Commun. 2016 Jun 29; 7: 11764.

GESTATIONAL DIABETES Pathway Scientist Marie-France Hivert, MD, has discovered that gestational diabetes differs from one woman to another, and the different causes lead to different outcomes for women and their children. Powe et al. Diabetes Care. 2016 Jun; 39(6): 1052-5.

DIABETES COMPLICATIONS Pathway Scientist Michael Dennis, PhD, has identified a master regulator of diabetic retinopathy, the leading cause of blindness in working age American adults. Moore et al. Cell Signal. 2016 May; 28(5): 384-90.

10

Pathway ScientistsDrive ProgressCOMMUNICATING ADVANCES TO MOVE THE FIELD FORWARD Science succeeds by building on the collective knowledge of the field. Communicating results— through publications and presentations—is how scientists share their findings with their peers and drive progress. Pathway scientists collectively have published nearly 40 research papers and reviews. In 2016 alone, they published 22 original research manuscripts and four reviews, and delivered 147 presentations. In addition, all of the awardees presented their research at the American Diabetes Association’s Scientific Sessions, the world’s largest diabetes meeting.

“AstraZeneca is committed to pushing the boundaries of science to discover life-changing medicines. A big part of that commitment has been our support of the Pathway to Stop Diabetes program. The support of these up-and-coming researchers is critical to advance the science for the treatment of diabetes.”

— Jim McDermott, Vice President, Medical Affairs–Diabetes, AstraZeneca

Above: 2015 Pathway Visionary awardee Mayland Chang, PhD (right), talks with Mentor Advisory Group member Lawrence Chan, MD, during the 2016 Pathway Symposium in New Orleans.11

SELECT 2016 PUBLICATIONS Soares MA, Cohen OD, Low YC, Sartor RA, Ellison T, Anil U, Anzai L, Chang JB, Saadeh PB, Rabbani PS, Ceradini DJ. Restoration of Nrf2 signaling normalizes the regenerative niche. Diabetes. 2016 Mar; 65(3): 633-46.

Miller WP, Mihailescu ML, Yang C, Barber AJ, Kimball SR, Jefferson LS, Dennis MD. The translational repressor 4E-BP1 contributes to diabetes-induced visual dysfunction. Invest Ophthalmol Vis Sci 2016 Mar; 57(3): 1327-37.

Szodoray P, Stanford SM, Molberg Ø, Munthe LA, Bottini N, Nakken B. T-helper signals restore B-cell receptor signaling in autoreactive anergic B cells by upregulating CD45 phosphatase activity. J Allergy Clin Immunol. 2016 Apr 4.

White PJ, Lapworth AL, An J, Wang L, McGarrah RW, Stevens RD, Ilkayeva O, George T, Muehlbauer MJ, Bain JR, Trimmer JK, Brosnan MJ, Rolph TP, Newgard CB. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export. Mol Metab. 2016 Apr 22; 5(7): 538-51.

Ye Y, Yu J, Wang C, Nguyen NY, Walker GM, Buse JB, Gu Z. Microneedles integrated with pancreatic cells and synthetic glucose-signal amplifiers for smart insulin delivery. Adv Mater. 2016 Apr; 28(16): 3115-21.

Tang JC, Drokhlyansky E, Etemad B, Rudolph S, Guo B, Wang S, Ellis EG, Li JZ, Cepko CL. Detection and manipulation of live antigen-expressing cells using conditionally stable nanobodies. eLife. 2016; May 20; 5.

Peck BC, Sincavage J, Feinstein S, Mah AT, Simmons JG, Lund PK, Sethupathy P. miR-30 family controls proliferation and differentiation of intestinal epithelial cell models by directing a broad gene expression program that includes SOX9 and the ubiquitin ligase pathway. J Biol Chem. 2016 Jul 29; 291(31): 15975-84.

Leib DE, Knight ZA. Rapid sensing of dietary amino acid deficiency does not require GCN2. Cell Reports. 2016, August 23; 16(8): 2051-2.

Kim HE, Grant AR, Simic MS, Kohnz R, Nomura DK, Durieux J, Riera CE, Sanchez M, Kapernick E, Wolff S, Dillin A. Lipid biosynthesis coordinates a mitochondrial to cytosolic stress response. Cell. 2016 Sep 8; 166(6): 1539-1552.e16.

Babon JA, DeNicola ME, Blodgett DM, Crèvecoeur I, Buttrick TS, Maehr R, Bottino R, Naji A, Kaddis J, Elyaman W, James EA, Haliyur R, Brissova M, Overbergh L, Mathieu C, Delong T, Haskins K, Pugliese A, Campbell-Thompson M, Mathews C, Atkinson MA, Powers AC, Harlan DM, Kent SC. Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes. Nat Med. 2016 Oct 31.

12

Pathway Accelerates Diabetes Research“Novo Nordisk is dedicated to working on excellence in diabetes and diabetes research. And this program, working together with the American Diabetes Association and supporting young investigators, is important for the future. It’s important for nurturing talent. It’s important also for supporting science that will increase the understanding we have of the diabetes disease, but also will hopefully lead to better therapies for people with diabetes.”

--Peter Kurtzhals, PhD, Senior Vice President and Head of Global Research, Novo Nordisk Inc.

“I think Sanofi engaged in Pathway’s program very early on for a very simple reason. And that is, compared to other disease areas, research in diabetes was actually quite meager, at least from a funding perspective. It really gives the investigator—the recipient of the grant—time to focus on what matters the most, and that is, really, to do the science.”

--Philip Larsen, MD, PhD, Vice President and Global Head of Diabetes Research and Translational Medicine, Sanofi

13 Above: 2016 Pathway Initiator awardee Phillip J. White, PhD (right), talks with 2016 Pathway Visionary awardee Andrew Scharenberg, MD, at the 2016 Pathway Symposium in New Orleans. Right: Mentor Advisory Group members David M. Harlan, MD (left), and Christopher J. Rhodes, PhD, participate in the discussion at the 2016 Pathway Symposium.

Pathway to a Promising Future

“I decided to give to the Pathway to Stop Diabetes program because I wanted to be a part of something bigger than myself, something that will have a ripple effect and help many people. I also wanted to encourage the young scientists and let them know that others care about the important work they are doing.”

-- Gladyce Anderson, philanthropic supporter of Pathway to Stop Diabetes

Amylase (human pancreatic alpha-amylase) protein, digestive enzyme, responsible for the hydrolysis of starch into sugars. 3D illustration. Wireframe representation and semi-transparent surfaces. Credit: molekuul_be/Shutterstock

“We support the Pathway initiative because we are anxious to see diabetes research progress as quickly as possible, using the best young minds in the country. Research costs money and researchers should not be the ones worried about raising it. Pathway helps scientists stay fully focused on their work and offers us hope that cures are in sight.”

-- Eileen and Steven Cortese, founding philanthropic supporters of Pathway to Stop Diabetes

Announcing the 2017 Pathway ScientistsThis year, 106 institutions nominated Pathway candidates. Of these, six new awardees were selected. They represent the highest quality scientists proposing novel and bold approaches to conquer diabetes.

INITIATOR AWARDS

New Avenues to Avoid Hypoglycemia Jonathan N. Flak, PhD, University of Michigan, Ann Arbor, Mich. Project Title: Targeting the VMN to Understand Hypoglycemia Pathogenesis

Diabetes therapies often lead to the risk of hypoglycemia—blood glucose levels that are too low. Hypoglycemia is especially dangerous in individuals who lack the normal nervous system response that alerts them to low blood glucose levels. This condition, which is called “hypoglycemia-associated autonomic failure” (HAAF), causes more frequent and more severe hypoglycemic episodes. This study will explore the role of the brain in development of HAAF. The results will identify potential treatment or prevention targets for HAAF and may also reveal previously unknown mechanisms that regulate glycemic control in diabetes. The Role of Gut Bacteria in T1D Risk Aleksandar David Kostic, PhD, Joslin Diabetes Center, Boston Project Title: Generation of an In Vivo System for Dissection of the Human Type 1 Diabetes-associated Microbiome

The bacteria that inhabit the intestinal tract may contribute to development of T1D. This project will explore whether gut microbes produce a stimulus that causes islet autoimmunity. The study aims to identify particular microbe species, genes, and metabolites that impact the immune system and metabolism in such a way that either promotes or prevents T1D. Specific species associated with T1D will be identified and introduced into animal models to induce autoimmune diabetes. Then the investigators will directly target the microbiota therapeutically in a way that could be translatable to human disease. Targeting the mechanisms by which these microbes impact disease offers a potential new, widely accessible public health approach to preventing T1D.

ACCELERATOR AWARDS

The Impact of Fat-Derived Factors on Glucose Levels Paul Cohen, MD, PhD, The Rockefeller University, New York Project Title: Dissecting the Role of Beige Fat in Metabolic Homeostasis

Not all fat cells are the same. Most of the fat tissue in the body is composed of white fat cells that are primarily used for storage of excess energy. In the obese state, white fat cells become inflamed and contribute to diabetes. In contrast, brown fat cells dissipate energy as heat and protect against obesity and diabetes. Beige fat cells are present within white fat. They share many properties with brown fat, and, as a result, are an interesting target for modulating metabolism. This study will test whether factors present in beige fat can reduce glucose production by the liver, thereby lowering blood glucose levels. The results could facilitate the development of novel mechanism-based therapies to treat diabetes and other obesity-associated diseases.

17

Announcing the 2017 Pathway ScientistsThis year, 106 institutions nominated Pathway candidates. Of these, six new awardees were selected. They represent the highest quality scientists proposing novel and bold approaches to conquer diabetes.

ACCELERATOR AWARDS (CONTINUED)

The Brain’s Role in Glucose Regulation Sarah A. Stanley, MD, PhD, Icahn School of Medicine at Mount Sinai, New York Project Title: Central Nervous System Regulation of Glucose Metabolism

The brain is a crucial part of the complex system that regulates blood glucose levels. Defects in these responses limit therapy in T1D and may contribute to T2D. This study examines regions of the brain that may link hormone responses and emotion. These areas may contribute to glucose regulation through circuits linked to the pancreas. The investigators will use novel techniques to determine the contribution of a specific population of glucose-sensing neurons to glucose metabolism and diabetes. With this foundation, future studies will explore whether restoring glucose responses in these neurons can prevent or reverse diabetes and its complications.

VISIONARY AWARDS

Engineering a Minimally Invasive Continuous Glucose Monitoring Patch Sumita Pennathur, PhD, University of California, Santa Barbara, Calif. Project Title: Untethering Diabetes Through Innovative Engineering

Achievement of good glucose control in people with diabetes depends on frequent self-monitoring of blood glucose values and appropriate adjustment and administration of therapeutics. Current developments in continuous glucose monitoring (CGM) strive to provide more precise readings with convenient and pain-free devices. This project aims to apply novel engineering approaches to develop a painless, minimally invasive, accurate, and disposable CGM patch. Advances like these will be critical for bringing the benefits of CGM to more people with diabetes. A New Approach to Reversing Diabetes Complications David A. Spiegel, MD, PhD, Yale University School of Medicine, New Haven, Conn. Project Title: Targeting Glucosepane Crosslinks in Diabetes

Glucosepane is a product in cells that results from interactions between proteins and glucose. It occurs naturally in many cellular proteins. Because glucose levels are high in people with diabetes, glucosepane levels are 20 times higher in people with diabetes than those without. High glucosepane is an independent risk factor for the onset of complications of diabetes, including nephropathy, retinopathy, and neuropathy. This project aims to determine the extent of glucosepane modifications in tissues throughout the body, the effects of these modifications, and mechanisms by which glucosepane formation can be altered. The idea is that preventing or reversing glucosepane formation may have the potential to undo diabetes-associated tissue damage.

18

The Mentor Advisory GroupEminent leaders in diabetes research serve on the Pathway to Stop Diabetes Mentor Advisory Group. They seek in the Pathway applicants the core elements for exceptional science: rigorous thought processes, keen intellect, and capacity for innovation, creativity, and productivity. And they serve as mentors to the awardees throughout the duration of their grants.

C. Ronald Kahn, MD Chair, Mentor Advisory Group Joslin Diabetes Center and Harvard Medical School, Boston

Domenico Accili, MD Columbia University Medical Center, New York

Barbara J. Anderson, PhD Baylor College of Medicine, Houston

Mark S. Anderson, MD, PhD University of California, San Francisco

Mark A. Atkinson, PhD The University of Florida, Gainesville, Fla.

Richard N. Bergman, PhD Cedars-Sinai Medical Center, Los Angeles

Morris J. Birnbaum, MD, PhD Pfizer Inc., Cambridge, Mass.

Charles Burant, MD, PhD University of Michigan Medical School, Ann Arbor, Mich.

John B. Buse, MD, PhD University of North Carolina School of Medicine, Chapel Hill, N.C.

Lawrence Chan, MD Baylor College of Medicine, Houston

Silvia Corvera, MD University of Massachusetts Medical School, Worcester, Mass.

Robert H. Eckel, MD University of Colorado Anschutz Medical Campus, Aurora, Colo.

Michael S. German, MD University of California, San Francisco

Margaret Grey, DrPH, RN, FAAN Yale University School of Nursing, New Haven, Conn.

David M. Harlan, MD University of Massachusetts Medical School, Worcester, Mass.

Barbara V. Howard, PhD MedStar Research Institute and Georgetown University, Hyattsville, Md.

19

The Mentor Advisory GroupEminent leaders in diabetes research serve on the Pathway to Stop Diabetes Mentor Advisory Group. They seek in the Pathway applicants the core elements for exceptional science: rigorous thought processes, keen intellect, and capacity for innovation, creativity, and productivity. And they serve as mentors to the awardees throughout the duration of their grants.

Barbara Kahn, MD Beth Israel Deaconess Medical Center, Boston

Steven E. Kahn, MB, ChB VA Puget Sound Health Care System and University of Washington School of Medicine, Seattle

Martin G. Myers, MD, PhD University of Michigan, Ann Arbor, Mich.

Christopher B. Newgard, PhD Duke University, Durham, N.C.

Alvin C. Powers, MD Vanderbilt University School of Medicine, Nashville, Tenn.

Susan E. Quaggin, MD Northwestern University Feinberg School of Medicine, Chicago

Christopher J. Rhodes, PhD MedImmune, LLC, Gaithersburg, Md.

Stephen S. Rich, PhD University of Virginia School of Medicine, Charlottesville, Va.

Alan R. Salteil, PhD University of California, San Diego, School of Medicine, La Jolla, Calif.

Jean E. Schaffer, MD Washington University School of Medicine, St. Louis

Philipp E. Scherer, PhD University of Texas Southwestern Medical Center, Dallas

Elizabeth R. Seaquist, MD University of Minnesota, Minneapolis, Minn.

Randy J. Seeley, PhD University of Michigan, Ann Arbor, Mich.

Gerald I. Shulman, MD, PhD Yale University School of Medicine, New Haven, Conn.

20

Corporate Sponsors and Philanthropic Supporters*

THE AMERICAN DIABETES ASSOCIATION RECOGNIZES THE PATHWAY TO STOP DIABETES FOUNDING CORPORATE SPONSORS, NOVO NORDISK, SANOFI, THE ELI LILLY AND COMPANY FOUNDATION, AND ASTRAZENECA, FOR THE GENEROUS CONTRIBUTIONS THAT ENSURED THE INITIATIVE’S SUCCESSFUL LAUNCH.

VISIONARY ($15 million and above)

ACCELERATOR ($10–15 million)

INITIATOR ($5–10 million)

BENEFACTOR ($2–5 million)

CORPORATE SPONSORS

Lilly Diabetes challenges other corporations and foundations to support Pathway to Stop Diabetes. We are excited to announce a unique matching gift program for Pathway donations received from new corporate and foundation donors in 2017. Lilly will contribute up to $500,000 in matching funds for corporations and foundations that have not donated in the previous calendar year.

For More Information Corporations should contact: Judy Lewis jlewis@diabetes.org 1-800-676-4065, ext. 1416

Family foundations should contact: Elaine Curran ecurran@diabetes.org 1-800-676-4065, ext. 3413

MATCHING GIFT PROGRAM

21

The Association extends deep appreciation for the generosity of the corporate sponsors and philanthropic supporters who have made the Pathway to Stop Diabetes initiative possible.

VISIONARY ($1 million and above)

Pete and Linda Cummin

Peter and Valerie** Kompaniez

Drs. Karen Talmadge and John Fiddes

Don and Arleen Wagner

ACCELERATOR ($100K- 999,999)

Mr. and Mrs. Irvin Angel

Alan and Elaine Armer, Trust

Mr. and Mrs. Joseph C. Cook Jr.

Ginger and Jack Graham

Mr. Douglas C. Hepper

Louise S. Hoffman

George and Judy Huntley

Ann E. Juster**

Dr. Orville G. Kolterman and Mrs. Gayle Lorenzi-Kolterman

Mr. and Mrs. James W. Quinn

Dr. and Mrs. Robert E. Sevier

Ralph and Laurie Yates

PHILANTHROPIC SUPPORTERS

BENEFACTOR ($2–5 million)

INITIATOR ($10K–99,999)

Gladyce Anderson

Vaneeda and Robert Bennett

Drs. David and Jane Bloomgarden

Elly and Roger Brtva

Eileen and Steven Cortese

Mara Darsow and Anthony Moreau

Richard J. Farber and Janet M. Leahy

Vivian and Sarita Fonseca

John Griffin and Lynn Knaupp

Dr. and Mrs. Robert R. Henry

Dwight Holing and Annie Notthoff

Dr. Emily Holing and Mr. Bill Dillon

S. Daniel and Cynthia Johnson

Dr. David M. Kendall

Alice and Cortland Knipe Charitable Trust

Karmeen Kulkarni

Lebherz Family Foundation

Wendell E. Mayes Jr., PhD

Dr. Dinesh Patel and Mrs. Kalpana Patel

Nan and Robert Ratner

Robert Singley

Bess Weatherman

*Contributions through 12/31/2016 **Deceased 22

2451 Crystal Drive, Suite 900 | Arlington, VA 222021-800-DIABETES diabetes.org