About

Dr. Siri Atma W. Greeley, MD, PhD, is an Associate Professor of Pediatrics and Medicine at the University of Chicago and serves as a Principal Investigator for studies on Neonatal Diabetes at the Kovler Diabetes Center. He is a pediatric endocrinologist specializing in the treatment of infants, children, and teens with all types of diabetes. Dr. Greeley's research focuses on the classification of diabetes type in individual patients, with a particular interest in monogenic diabetes. His work aims to improve understanding and treatment of diabetes in young patients through precise diagnosis and tailored therapeutic approaches.

Research topics

• Medicine
• Endocrinology
• Internal medicine
• Intensive care medicine
• Political Science
• Genetics
• Biology
• Pediatrics
• Family medicine
• Pathology
• Computational biology
• Bioinformatics
• Surgery
• Physical therapy

Selected publications

• Anxiety, social responsiveness, and grit among patients with KCNJ11-related neonatal diabetes compared to unaffected siblings

  Acta Diabetologica · 2026-01-27

  articleOpen accessSenior authorCorresponding

  AIMS: Neonatal diabetes mellitus (NDM) occurs before 6-12 months of age and is commonly caused by activating mutations in KCNJ11 (KCNJ11-NDM) or ABCC8. Because of brain expression of these mutant ATP-dependent potassium channels, a spectrum of divergent neurodevelopmental difficulties have been described, including developmental delay, epilepsy, and neonatal diabetes (DEND). However, information on anxiety, social responsiveness, and grit is limited. METHODS: Individuals with KCNJ11-NDM (N = 12) and their unaffected siblings (N = 12) were recruited through the University of Chicago Monogenic Diabetes Registry and participants or their parent/caregiver completedthe Screen for Adult/Child Anxiety Related Disorder (SCAARED/SCARED), the Social Responsiveness Scale, Second Edition (SRS-2), and the Grit Scale. RESULTS: Mean SRS-2 scores were significantly different between KCNJ11-NDM and sibling controls (P = <0.001 ), with 7/10 affected participants, and 0 /11 siblings, having scores suggestive of autism spectrum disorder (ASD). Differences in anxiety (P = 0.69) and grit (P = 0.46) were not significant when compared to sibling controls; however, 58% (7/12) of KCNJ11-NDM participants and 40% (4/10) of sibling controls had scores indicating an anxiety disorder by either self- or parent-report. CONCLUSIONS: Our results agree with previous studies suggesting significant difficulties with social functioning in KCNJ11-NDM, with 7/10 participants having scores suggestive of ASD, strongly reinforcing the need for early neurodevelopmental screening to allow for prompt support. Our report adds to the knowledge of this population in finding robust grit scores but with a high level of anxiety in both KCNJ11-NDM and unaffected siblings. Although families affected by KCNJ11-NDM may have a high risk of anxiety disorders, it is encouraging that affected and unaffected children exhibit robust self-resiliency that will help support functioning through the challenges of life. Study of additional individuals will help to clarify specific challenges, long-term outcomes, and best approaches for monitoring and support.

  PublisherOA PDFDOI

• Advancing Monogenic Diabetes Research and Clinical Care by Creating a Data Commons: The Precision Diabetes Consortium (PREDICT)

  Journal of Diabetes Science and Technology · 2025-01-09 · 1 citations

  articleOpen access

  Monogenic diabetes mellitus (MDM) is a group of relatively rare disorders caused by pathogenic variants in key genes that result in hyperglycemia. Lack of identified cases, along with absent data standards, and limited collaboration across institutions have hindered research progress. To address this, the UChicago Monogenic Diabetes Registry (UCMDMR) and UChicago Data for the Common Good (D4CG) created a national consortium of MDM research institutions called the PREcision DIabetes ConsorTium (PREDICT). Following the D4CG model, PREDICT has successfully established a multicenter MDM data commons. PREDICT has created a consensus data dictionary that will be utilized to address critical gaps in understanding of these rare types of diabetes. This approach may be useful for other rare conditions that would benefit from access to harmonized pooled data.

  PublisherOA PDFDOI

• Approach to the Patient: Mitochondrial Diabetes: Contemporary Cases and a Precision Medicine Approach

  The Journal of Clinical Endocrinology & Metabolism · 2025-12-30 · 1 citations

  articleOpen access

  Maternally inherited diabetes and deafness (MIDD) syndrome is a rare form of monogenic diabetes most often caused by the pathogenic m.3243A > G mutation in the mitochondrial tRNALeu (UUR) gene, MT-TL1. Mutations causing MIDD are also associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. This paper analyzes the data of 15 probands with mitochondrial diabetes enrolled in the University of Chicago Monogenic Diabetes Registry, all of whom have confirmed pathogenic variants, primarily m.3243A > G. Three of these probands (3/15) were selected for detailed case studies and pedigree analysis. Among the total cohort, sensorineural hearing loss (80%) and muscle weakness (53%) were frequent comorbidities, and all tested individuals were negative for islet autoantibodies. Treatment regimens included insulin and sulfonylureas, with some reporting use of biguanides despite safety concerns related to mitochondrial dysfunction. Three probands noted subjective improvement with mitochondrial cocktail supplementation. Familial heteroplasmy testing revealed significant inter- and intrafamilial variability. This cohort represents 1 of the largest clinically characterized US populations with mitochondrial diabetes and underscores the importance of urine-based heteroplasmy testing and personalized management strategies informed by mitochondrial pathophysiology.

  PublisherOA PDFDOI

• Creation and Evaluation of a Research Participant Portal for the University of Chicago Monogenic Diabetes Registry

  Journal of Diabetes Science and Technology · 2025-12-11

  articleOpen access

  The University of Chicago Monogenic Diabetes Registry (UCMDR) developed a participant portal to enhance engagement and data completeness in a large, longitudinal research study. Built in collaboration with the Center for Research Informatics (CRI), the portal integrates with REDCap to provide secure survey access, document exchange, and communication. Since its launch, 40% of invited participants have activated accounts. Among new enrollees, 88% of portal users completed their baseline survey, up from a historical 60%. Portal activation was higher among female participants ( P &lt; .01), with no significant differences by age or income. Overall portal feature use was modest, possibly reflecting lower adoption among historical participants accustomed to legacy processes. These findings support the feasibility of research participant portals while highlighting opportunities to improve equitable engagement and functionality.

  PublisherOA PDFDOI

• Sleep patterns in adults and children with less common forms of diabetes

  Frontiers in Endocrinology · 2025-10-13

  reviewOpen access

  Objective: To review the current evidence on sleep patterns in relation to glucose control in adults and children with type 1 diabetes (T1DM) and monogenic diabetes. Methods: We searched for the literature pertaining to T1DM and monogenic diabetes with reported sleep patterns, along with glycemic control, in PubMed. This review aimed to examine the current evidence on the relationship between sleep patterns and diabetes management and possible mediating mechanisms for this relationship in adults and children with T1DM and monogenic diabetes. We reviewed articles published from inception until 2023. Results: Twenty-five clinical studies met the eligibility criteria and were included. Children with T1DM with higher sleep variability had higher glucose levels, and those with higher glucose variability had more sleep disruptions. Comparing children with suboptimal [hemoglobin A1c (HbA1c) ≥ 7.5%] and optimal glucose control, those with suboptimal control had shorter sleep duration. There was no higher prevalence of obstructive sleep apnea (OSA) in children with T1DM compared to controls, but in T1DM, those who had OSA had higher glucose levels. Adults with T1DM had a high prevalence of poor sleep quality and were also sleeping less than the recommended hours for their age. Poor sleep quality and short sleep duration correlated with higher glycemic variability. First-generation automated insulin delivery systems did not improve sleep patterns in T1DM, but other strategies, including coaching and counseling, proved to be effective. Monogenic diabetes data also suggest poor sleep quality, short sleep duration, and high rates of sleep apnea. Conclusion: T1DM subjects seem to have worse sleep patterns, especially those with suboptimal glucose control. Monogenic diabetes data are limited, but they also suggest poor sleep patterns. Rigorous interventional studies are needed to further elucidate the sleep-diabetes relationship. Future research could provide insights into strategies that could effectively improve sleep in people living with diabetes.

  PublisherOA PDFDOI

• &lt;b&gt;Smaller pancreas volume in insulin-dependent monogenic diabetes&lt;/b&gt;

  2025-05-22

  preprintOpen access

  &lt;p dir="ltr"&gt;Individuals with type 1 diabetes (T1D) or permanent neonatal diabetes (PND) due to an &lt;i&gt;INS&lt;/i&gt; gene mutation have a marked reduction in pancreas volume by MRI compared to control individuals with no diabetes (ND). One possible explanation for this is loss of islet-acinar insulin signaling in these forms of severe insulin deficiency. To test the hypothesis that insulin deficiency drives the loss of pancreas volume in diabetes, we used a standardized and validated MRI protocol to measure pancreas volumes in individuals with various forms of monogenic diabetes (HNF4A-MODY, GCK-MODY, HNF1A-MODY, HNF1B-MODY, INS-MODY, or INS-PND, n = 37), and compared their pancreas volumes with those of previously reported individuals with T1D (n = 93) or healthy ND controls (n = 90). Across all monogenic diabetes groups, individuals on insulin therapy had significantly smaller pancreas volume compared to those not requiring insulin. These results support the hypothesis that insulin signaling to the exocrine pancreas determines pancreas volume in multiple types of diabetes.&lt;/p&gt;

  PublisherOA PDFDOI

• 2130-LB: Novel Insulin Gene Variants in Antibody-Negative Adult-Onset Diabetes

  Diabetes · 2025-06-13

  article

  Introduction and Objective: Insulin gene (INS) variants are a rare cause of monogenic diabetes, with clinical presentations including (1) permanent or transient neonatal diabetes and (2) adolescent or adult-onset diabetes sometimes referred to as maturity onset diabetes of the young (INS-MODY/MODY10). Here we report four previously undescribed INS variants in individuals with atypical adult-onset diabetes. Methods: Four rare (0-3 copies in gnomAD v.4.1) INS variants were characterized in Rare and Atypical Diabetes Network (RADIANT) study participants as well as a RADIANT investigator’s clinical patient. Selected variants were studied in vitro for splicing in INS-1 cells and/or trafficking in Min6/HEK293T cells. Results: Three variants predicted to alter proinsulin sequence were identified in three index cases and the daughter of one index case. All were nonobese and diagnosed with antibody-negative diabetes in their 20s and 30s (current HbA1c range 5.3% on lifestyle alone, to 7.8% on insulin). A fourth variant was found in the non-RADIANT patient, who was diagnosed with diabetes in her 50s (lean, antibody-negative, current HbA1c 6.7% on insulin). The variants were: a proximal intronic variant c.188-11C&amp;gt;A with in vitro functional evidence that enlarges the C-peptide region by three amino acids and impairs proinsulin secretion; a missense variant (p.P25S) that blocks proinsulin secretion in vitro; and two frameshift variants (p.A74Efs*57 and p.L86Rfs*36) lacking the insulin A-chain. Conclusion: This case series contributes to the growing literature on the role of rare heterozygous INS variants in adult-onset diabetes. We describe three variants that structurally alter mature insulin and one of the first reports of a proinsulin C-peptide-altering variant that does not generate an extra cysteine or create a frameshift, yet disrupts proinsulin trafficking. The identification of greater numbers of cases with INS variants will help clarify severity and penetrance of diabetes. Disclosure D. Broome: Research Support; Fractyl Health, Inc., Sanofi, T1D Exchange, Rhythm Pharmaceuticals, Inc, Novo Nordisk. K.A. Maloney: None. S.W. Greeley: Advisory Panel; Sanofi. S. Park: None. E.D. Szmuilowicz: None. L.K. Billings: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Sanofi. Consultant; Dexcom, Inc. Advisory Panel; Bayer Pharmaceuticals, Inc. Consultant; Xeris Pharmaceuticals, Inc. Advisory Panel; Amgen Inc. Consultant; Pfizer Inc. L.H. Philipson: Other Relationship; Novo Nordisk, Dompé, Diasome Pharmaceuticals, Vertex Pharmaceuticals Incorporated. Consultant; Amylyx. Other Relationship; Bayer Pharmaceuticals, Inc, Provention Bio, Inc, Provention Bio, Inc, Microbion, Microbion. S.E. Kahn: Advisory Panel; Amgen Inc, AltPep, Biomea Fusion. Research Support; Corcept Therapeutics. Advisory Panel; Eli Lilly and Company, Merck &amp; Co., Inc. Consultant; Neurimmune. Advisory Panel; Novo Nordisk, Oramed Pharmaceuticals. P. Arvan: None. N. Rasouli: Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company. T.I. Pollin: None. Funding NIH (U54 DK118612)

  PublisherDOI

• Antibody-Positive Type 1 Diabetes in a Family With a Pathogenic <i>HNF1A</i>-MODY Variant and Variable Age of Onset

  JCEM Case Reports · 2025-09-25

  articleOpen access

  Abstract Monogenic diabetes (MD) is a relatively rare and heterogeneous group of disorders caused by pathogenic single-gene variants or abnormalities resulting in hyperglycemia. MD represents approximately 3.5% of all diabetes cases diagnosed before age 35 years, though it is possible for MD to develop at later ages. MD diagnoses have implications for precision therapy and cascade genetic testing. A hallmark characteristic suggesting MD is a multigenerational family history of nonobese diabetes diagnosed before age 35 with an autosomal dominant inheritance. However, even with a known family history of genetically confirmed MD, it is possible for an individual within that family to have a different form of diabetes. Here, we present a case from the University of Chicago Monogenic Diabetes Registry of an individual with antibody-positive type 1 diabetes in a family with a history of a genetically confirmed known pathogenic HNF1A variant causing maturity-onset diabetes of the young (MODY) with variable age of onset in affected individuals. This family pedigree showcases that HNF1A-MODY can develop at any age and illustrates the importance of every individual receiving a thorough work-up for accurate diabetes classification, including obtaining antibody testing and genetic testing, when indicated, to provide optimal treatment and management.

  PublisherOA PDFDOI

• Smaller Pancreas Volume in Insulin-Dependent Monogenic Diabetes

  Diabetes · 2025-05-22 · 1 citations

  articleOpen access

  Individuals with type 1 diabetes (T1D) or permanent neonatal diabetes (PND) due to an INS gene mutation (INS-PND) have a marked reduction in pancreas volume by MRI compared with control individuals with no diabetes (ND). One possible explanation for this is loss of islet-acinar insulin signaling in these forms of severe insulin deficiency. To test the hypothesis that insulin deficiency drives the loss of pancreas volume in diabetes, we used a standardized and validated MRI protocol to measure pancreas volumes in individuals with various forms of monogenic diabetes, including maturity-onset diabetes of the young (MODY) and PND (HNF4A-MODY, GCK-MODY, HNF1A-MODY, HNF1B-MODY, INS-MODY, or INS-PND; n = 37), and compared their pancreas volumes with those of previously reported individuals with T1D (n = 93) or healthy control participants with ND (n = 90). Across all monogenic diabetes groups, individuals receiving insulin therapy had significantly smaller pancreas volume compared with those not requiring insulin. These results support the hypothesis that insulin signaling to the exocrine pancreas determines pancreas volume in multiple types of diabetes. ARTICLE HIGHLIGHTS: Individuals with type 1 diabetes (T1D) have a markedly smaller pancreas, but the mechanism responsible for the reduction in size is unknown. How pancreas volume differs in individuals with specific forms of monogenic diabetes and how pancreas volume relates to the severity of insulin deficiency are unknown. Measured by MRI, individuals with permanent neonatal diabetes due to an INS gene mutation (INS-PND) or the HNF1B gene associated with maturity-onset diabetes of the young had smaller pancreas than individuals without diabetes. Across all types of monogenic diabetes, individuals receiving insulin replacement therapy had smaller pancreas than individuals not using insulin. These results support the conclusion that insulin deficiency is a major factor contributing to changes in pancreas volume in T1D, INS-PND, and other forms of monogenic diabetes.

  PublisherOA PDFDOI

• &lt;b&gt;Smaller pancreas volume in insulin-dependent monogenic diabetes&lt;/b&gt;

  2025-05-22

  preprintOpen access

  &lt;p dir="ltr"&gt;Individuals with type 1 diabetes (T1D) or permanent neonatal diabetes (PND) due to an &lt;i&gt;INS&lt;/i&gt; gene mutation have a marked reduction in pancreas volume by MRI compared to control individuals with no diabetes (ND). One possible explanation for this is loss of islet-acinar insulin signaling in these forms of severe insulin deficiency. To test the hypothesis that insulin deficiency drives the loss of pancreas volume in diabetes, we used a standardized and validated MRI protocol to measure pancreas volumes in individuals with various forms of monogenic diabetes (HNF4A-MODY, GCK-MODY, HNF1A-MODY, HNF1B-MODY, INS-MODY, or INS-PND, n = 37), and compared their pancreas volumes with those of previously reported individuals with T1D (n = 93) or healthy ND controls (n = 90). Across all monogenic diabetes groups, individuals on insulin therapy had significantly smaller pancreas volume compared to those not requiring insulin. These results support the hypothesis that insulin signaling to the exocrine pancreas determines pancreas volume in multiple types of diabetes.&lt;/p&gt;

  PublisherDOI

Recent grants

• Monogenic Diabetes: Next Generation Diagnosis, Treatment and Complications

  NIH · $4.7M · 2016–2024

• NIH Grant K23DK094866

  NIH · $515k · 2015

• NIH Grant R03DK103096

  NIH · $149k · 2017

Frequent coauthors

• Louis H. Philipson

  University of Chicago

  83 shared

• Rochelle N. Naylor

  University of Chicago

  63 shared

• Lisa R. Letourneau

  University of Chicago

  54 shared

• Cécile Saint‐Martin

  Assistance Publique – Hôpitaux de Paris

  53 shared

• Jacques Beltrand

  Sorbonne Paris Cité

  53 shared

• Norbert Stefan

  Deutsches Diabetes-Zentrum e.V.

  52 shared

• Feifei Cheng

  Dalian Medical University

  51 shared

• Róbert Wágner

  Heinrich Heine University Düsseldorf

  50 shared

Labs

• Siri Atma W. Greeley LabPI

Education

• B.S., Chemistry and Bioengineering

  Columbia University

  1995

• Ph.D., Immunology

  University of Pennsylvania

  2002

• M.D.

  University of Pennsylvania

  2003

• M.D., Pediatrics

  The University of Chicago Comer Children's Hospital

  2006

• M.D., Pediatric Endocrinology

  The University of Chicago Comer Children's Hospital

  2009

Awards & honors

• 3rd DMDEA Gold Medal Oration Award Dr. Mohan’s Diabetes Educ…
• Early Career Development Award Central Society for Clinical…
• Ira Rosenthal Memorial Lecture University of Illinois at Chi…
• Lewis-Sebring Family Foundation Fellow in Diabetes Genetics…
• The George M. Eisenberg Foundation for Charities Excellence…