Steven M. Willi

faculty photo
Professor of Pediatrics (Endocrinology and Diabetes) at the Children's Hospital of Philadelphia
Department: Pediatrics

Contact information
Division of Endocrinology and Diabetes
The Children's Hospital of Philadelphia
3500 Civic Center Blvd
HUB for Clinical Collaboration, Room 7564
Philadelphia, PA 19104
Office: (215) 280-3874
Fax: (215) 590-3053
Lab: (267) 426-9218
Education:
BA (Chemistry)
Johns Hopkins University, 1981.
MD (Medicine)
Johns Hopkins University, 1985.
Post-Graduate Training
Resident in Pediatrics, The Children's Hospital of Philadelphia, 1985-1988.
Clinical Fellow in Endocrinology/Diabetes, The Children's Hospital of Philadelphia, 1988-1989.
Research Fellow in Endocrinology/Diabetes, The Children's Hospital of Philadelphia, 1989-1992.
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Description of Research Expertise

I am full-time faculty member at the University of Pennsylvania, a Pediatric Endocrinologist with a clinical research interest in the areas of pediatric diabetes and obesity. My ongoing research trials are designed to delay the progression of type 1 diabetes in new onset patients, assess new developments in type 1 diabetes treatment and examine the safety and pharmacokinetics of various medications for the treatment of type 2 diabetes and obesity in children. I am also conducting a number of observational clinical trials assessing trends in diabetes treatment and complications in pediatric and young adult populations. I received a Clinical Associate Physician Award from NIH to study the mechanisms of insulin resistance in pediatric type 2 diabetes, and have reviewed career development award grants for NIH for many years. I am currently Program Director and PI of a K12 Program for Pediatric Endocrinologists purseing a career in diabetes research. My contributions to the field of medicine are summarized below:

Optimization of T1DM therapy: Patients with T1DM are at risk for acute complications including severe hypoglycemia and diabetic ketoacidosis. In addition, long-term elevated blood glucose is associated with microvascular complications including retinopathy, neuropathy, and nephropathy. I have leveraged large cooperative databases of T1DM patients to investigate risk factors for acute complications and have demonstrated that non-white race and socioeconomic deprivation are significant barriers to optimal care. In addition, I have demonstrated in clinical trials that continuous insulin pump therapy leads to improved glucose control compared with traditional injection therapy.

Immunomodulatory therapies in new-onset T1DM: While T1DM can be managed as a chronic disease with subcutaneous insulin administration, this therapy is challenging and burdensome for patients and their families. Few patients are able to consistently attain good glycemic control, putting them at risk for long-term complications. I have been a co-investigator in several trials designed to modulate the immune attack in T1DM, with the goal of preserving β-cell function. In particular, therapies that specifically target T cells show promise and are now being evaluated in high-risk relatives of patients with T1DM.

Type 2 diabetes in youth: While historically, type 2 diabetes (T2DM) has been thought of as an adult disease, the ongoing obesity epidemic is leading to an increased prevalence of T2DM in youth. Emerging evidence suggests that the course of T2DM is more aggressive in children than in adults. I am a co-investigator in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study which demonstrated superior efficacy of metformin plus rosiglitazone compared with metformin plus lifestyle or metformin alone in maintaining target glycemic control. In a secondary analysis, my work led to the demonstration that this difference in efficacy is due to improved insulin sensitivity in the combined therapy group, while baseline insulin secretion is an independent predictor of disease progression. We also demonstrated that all three treatment modalities were safe and well-tolerated in youth, and that outcomes are strongly related to parental obesity and associated co-morbidities. In addition, leveraging data from the Pediatric Diabetes Consortium, I have helped define the presenting signs and symptoms of T2DM in youth, with notable findings including that 13% present in severe distress with either DKA or hyperglycemic hyperosmolar state and that children with T2DM quite often have significant social vulnerability due to poverty and low educational attainment of family members.

The role of pediatric obesity in CVD: Cardiovascular disease (CVD) generally presents during adulthood, but the antecedents of this adult disease may be detectable in childhood. Elevated lipid and blood pressure levels have been associated with an increased risk of cardiovascular disease, and these risk factors track from childhood into adulthood. Poor nutrition, a sedentary lifestyle, and genetic factors predispose to multiple CVD risk factors, including obesity, hyperlipidemia, and hypertension. CVD is the leading cause of mortality in the United States and is associated with the recent increase in obesity rates, which have tripled in youth since 1980. I have been interested in clinical and lifestyle interventions to ameliorate the effects of obesity on CVD risk for many years. My role as coinvestigator in the HEALTHY study has afforded the opportunity to examine the antecedents of cardiovascular disease in an at risk population, and explore the efficacy of a primary prevention strategy. My goal has been to increase knowledge of these risks in the hope of encouraging healthy behaviors for the purpose of improving cardiovascular health. I have been working with a number of collaborators in Bejing, China in the capacity of adviser to the education program for Maternal and Childhood Obesity Prevention and Management. I am assisting them in their endeavor to publish their data in high quality medical journals.

Description of Itmat Expertise

Dr. Willi is interested in therapeutics for type 1 and type 2 diabetes and has performed a number of physiologic studies in the etiology and characterization of diabetes in children. He has been caring for diabetes patients, designing clinical diabetes programming and conducting clinical diabetes research for over 25 years. During that time, he has been the recipient of a number of research grants from NIH, CDC and the FDA, as well as from industry and private foundations. He has served on the IRB and CRC Advisory Committees throughout his career. Recognition of Dr. Willi's clinical expertise is evident from his inclusion in "The Best Doctors in America", Marquis Who's Who, Castle Connolly’s Top Doctors and the Consumer Research Council's Guide to America's Top Pediatricians. He has been recognized as a clinical researcher by being asked to serve on numerous NIH/NIDDK Special Emphasis Panels, an Individual Fellowship Scientific Review Group at NHLBI, and a Special Advisory Panel to the United States Office of Human Research Protection. He has served on numerous Data Safety Monitoring Boards over the years, and is currently on the DSMB for the NIH Artificial Pancreas Trials. Current studies include trials on the delay of progression of type 1 diabetes and several trials to examine the therapeutic potential of novel agents and devices in the management of type 1 and type 2 diabetes in children.

Selected Publications

Van Name MA, Kanapka LG, DiMeglio LA, Miller KM, Albanese-O'Neill A, Commissariat P, Corathers SD, Harrington KR, Hilliard ME, Anderson BJ, Kelley JC, Laffel LM, MacLeish SA, Nathan BM, Tamborlane WV, Wadwa RP, Willi SM, Williams KM, Wintergerst KA, Woerner S, Wong JC, DeSalvo DJ. : Long-term Continuous Glucose Monitor Use in Very Young Children With Type 1 Diabetes: One-Year Results From the SENCE Study. J Diabetes Sci Technol. 17(4): 976-987, July 2023 Notes: doi: 10.1177/19322968221084667. Epub 2022 Mar 26.

Bacha F, El Ghormli L, Braffett BH, Shah AS, Marcovina SM, Levitt Katz LE, Willi SM, Caprio S, Dhaliwal R, Gidding SS; for the TODAY Study Group. : Candidate biomarkers as predictors of future kidney disease and cardiovascular dysfunction in adolescents with type 2 diabetes. Diabetes Res Clin Pract. 199: 110671, May 2023 Notes: doi: 10.1016/j.diabres.2023.110671. Epub 2023 Apr 15.

Laffel LM, Danne T, Klingensmith GJ, Tamborlane WV, Willi S, Zeitler P, Neubacher D, Marquard J; DINAMO Study Group.: Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial. Lancet Diabetes Endocrinol 11(3): 169-181, March 2023 Notes: doi: 10.1016/S2213-8587(22)00387-4.

Hitt TA, Hershey JA, Olivos-Stewart D, Forth E, Stuart F, Garren P, Mitchell J, Hawkes CP, Willi SM, Gettings JM.: The impact of fear of hypoglycaemia on sleep in adolescents with type 1 diabetes. Diabet Med Feb 2023 Notes: DOI: 10.1111/dme.15066.

Shah AS, Gidding SS, El Ghormli L, Tryggestad JB, Nadeau KJ, Bacha F, Levitt Katz LE, Willi SM, Lima J, Urbina EM; TODAY Study Group.: Relationship between Arterial Stiffness and Subsequent Cardiac Structure and Function in Young Adults with Youth-Onset Type 2 Diabetes: Results from the TODAY Study. J Am Soc Echocardiogr 35(6): 620-628, June 2022.

Van Name MA, Kanapka LG, DiMeglio LA, Miller KM, Albanese-O'Neill A, Commissariat P, Corathers SD, Harrington KR, Hilliard ME, Anderson BJ, Kelley JC, Laffel LM, MacLeish SA, Nathan BM, Tamborlane WV, Wadwa RP, Willi SM, Williams KM, Wintergerst KA, Woerner S, Wong JC, DeSalvo DJ.: Long-term Continuous Glucose Monitor Use in Very Young Children With Type 1 Diabetes: One-Year Results From the SENCE Study. J Diabetes Sci Technol Mar 2022.

Li G, Zhong L, Han L, Wang Y, Li B, Wang D, Zhao Y, Li Y, Zhang Q, Qi L, Speakman JR, Willi SM, Li M, Gao S.: Genetic variations in adiponectin levels and dietary patterns on metabolic health among children with normal weight versus obesity: the BCAMS study. Int J Obes (Lond) 46(2): 325-332, Feb 2022.

Gal JJ, Li Z, Willi SM, Riddell MC.: Association between high levels of physical activity and improved glucose control on active days in youth with type 1 diabetes. Pediatr Diabetes 2022.

Hawkes CP, Willi SM.: A trend towards an early increase in ketoacidosis at presentation of paediatric type 1 diabetes during the coronavirus-2019 pandemic. Diabet Med 38(4): e14461, April 2021 Notes: doi: 10.1111/dme.14461. Epub 2020 Dec 1.

Wu Y, Zhong L, Li G, Han L, Fu J, Li Y, Li L, Zhang Q, Guo Y, Xiao X, Qi L, Li M, Gao S, Willi SM.: Puberty Status Modifies the Effects of Genetic Variants, Lifestyle Factors and Their Interactions on Adiponectin: The BCAMS Study. Front Endocrinol (Lausanne) 12: 737459, Dec 2021.

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Last updated: 01/15/2024
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