Modeling Ketosis-Prone Diabetes Remission Via Diverse Mechanisms of Glucotoxicity

The goal of this study is to quantify day-to-day changes in blood glucose during treatment towards remission in ketosis-prone diabetes (KPDM) and describe them using a mathematical model of KPDM pathogenesis and remission.

Study Overview

• Status: Recruiting
• Conditions: Ketosis Prone Diabetes
• Intervention / Treatment: Device: Continuous Glucose Monitoring; Drug: Insulin

Detailed Description

Approximately half of newly diagnosed obese African Americans presenting with diabetic ketoacidosis (DKA) have clinical, metabolic and immunologic features of type 2 diabetes (T2D), also known as ketosis-prone diabetes (KPDM). Unlike patients with type 1 diabetes, with intensive insulin treatment, approximately 70% of patients with KPDM exhibit improved pancreatic β-cell function and insulin sensitivity to allow discontinuation of insulin therapy (indicating near-normoglycemia remission based on fasting blood glucose (FBG) < 130 mg/dl and HbA1c < 7% off insulin therapy during follow-up]). The clinical course of KPDM is variable, with the duration of remission ranging from 6 to 120 months. The origins of this variation in the ability to achieve remission and its duration are poorly understood.

It has been observed that a 20-hour infusion of glucose reduces pancreatic beta (β)-cell function in a KPDM patient, and ketotic relapse is often preceded by hyperglycemia. The researchers thus hypothesized that the differences between conventional T2D and KPDM may be explained by the presence of a reversible glucotoxicity process, which operates on the timescale of days. The researchers developed a preliminary mathematical model describing the pathogenesis and remission of KPDM using such a process. The researchers showed that, by changing the rate of this hypothesized glucotoxicity process, this model can produce a variety of clinical courses, describing both conventional T2D and KPDM with varying rates and durations of remission.

This study is a pilot study that will refine and validate this model using prospective clinical data with continuous glucose monitor (CGM) data from patients with KPDM.

Patients will receive standard-of-care treatment for their diabetes as per their treating physician. Insulin therapy is the standard of care after an episode of DKA. Therefore, all participants will be discharged on insulin. A CGM will be placed on these participants at discharge from the hospital until insulin discontinuation. Since many of these patients insulin needs decrease after discharge from the hospital, the study team will utilize CGM glucose readings to adjust insulin doses.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Priyathama Vellanki, MD, MS; Phone Number: (404) 778-1687; Email: priyathama.vellanki@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Recruiting
      • Grady Health System
    • Atlanta, Georgia, United States, 30308
      • Recruiting
      • Emory University Hospital Midtown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provide informed consent
• Have a BMI ≥ 28 kg/m2
• Be of African American ancestry
• Meet diagnostic criteria for DKA. Diagnostic criteria for DKA will include a plasma glucose > 250 mg/dl, a venous pH < 7.30, a serum bicarbonate < 18 mmol/l, and serum ketones (beta-hydroxy butyrate) > 1.5 mmol/L.

Exclusion Criteria:

• Significant medical or surgical illness including but not limited to myocardial ischemia, congestive heart failure, chronic peripheral venous insufficiency, chronic renal insufficiency, liver insufficiency (serum transaminases 3 times the upper limit of normal) and acute or chronic infectious processes
• Have recognized uncontrolled endocrine disorders such as hypercortisolism, acromegaly, or hyperthyroidism
• Anemia (hemoglobin < 12.5 g/dL for men, <11.5 gm/dL for women), bleeding disorders, or abnormalities in coagulation studies
• Pregnant
• Diagnosis of diabetes > 90 days before the presentation of DKA
• Unable to give consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous Glucose Monitoring with Adjusted Insulin Doses; Patients with ketosis-prone diabetes will wear a continuous glucose monitor (CGM) from the time of hospital discharge until insulin discontinuation. Insulin doses will be adjusted based on CGM glucose readings.	Device: Continuous Glucose Monitoring; After insulin discontinuation participants continue wearing their CGMs, for a total of 3 months.; Other Names: Freestyle Libre; Drug: Insulin; Participants will receive standard-of-care insulin treatment. Insulin dosing will be adjusted based on CGM glucose readings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantify Changes in Blood Glucose	The day-to-day changes in blood glucose in KPDM will be quantified using CGMs.	Up to 3 months
Development of Mathematical Models	The study team will adapt and develop mathematical models to describe the course of KPDM remission in each individual patient, i.e. the entire range of variation within the group of 12 participants.	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of Fit With Model Parameters and Duration of Remission	The study team will validate mathematical models to predict duration of remission.	Up to 3 months

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Priyathama Vellanki, MD, MS, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: type 2 diabetes; diabetic ketoacidosis
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Complications; Acid-Base Imbalance; Acidosis; Nutritional and Metabolic Diseases; Ketosis; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Insulins; Pancreatic Hormones; Proinsulin; Blood Chemical Analysis; Clinical Chemistry Tests; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Insulin; Continuous Glucose Monitoring
• Other Study ID Numbers: STUDY00008366; 2024P008641 (Other Identifier: Emory IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No