Lactate and Glycerol Contribution to Gluconeogenesis

NCT06955130 | Not Yet Recruiting DMC

• 1 other identifier: Pro2019002628
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

A major cause of increased blood glucose levels in type 2 diabetes (T2D) is increased hepatic gluconeogenesis (GNG), as the liver converts various substrates into glucose. Two of these substrates include glycerol, a molecule from fat, and lactate, a molecule that circulates in the blood. Our previously collected data suggest that glycerol's role in this process has been underestimated, so the investigators will directly compare the carbon contribution of glycerol and lactate to new glucose production under fasting conditions in patients with and without T2D. The investigators will also assess how glucagon, a hormone that raises blood glucose levels, impacts the conversion of glycerol and lactate to glucose. Enrolled participants will undergo three separate isotope tracer infusions with serial blood collections for liquid chromatography-mass spectrometry analysis. This research could identify new therapeutic drug targets that can lower blood glucose levels more directly and effectively.

Conditions

Type 2 Diabetes; Obesity; Healthy

Keywords

diabetes; glucose

Outcome Measures

Primary Outcomes (1)

• Carbon Contribution to Glucose Production

  Net carbon flux from glycerol and lactate to glucose will be measured using LC-MS of plasma glucose via 13C-enrichment after infusion of various metabolic tracers

  8 hours

Study Arms (3)

Glycerol

EXPERIMENTAL

Each subject will receive labeled 13C3-glycerol.

Drug: Glycerol

Lactate

EXPERIMENTAL

Each subject will receive labeled 13C3-lactate.

Drug: Lactate

Glucose

EXPERIMENTAL

Each subject will receive labeled 13C6-glucose.

Drug: Glucose

Interventions

Glycerol DRUG

Subjects will receive an infusion of glycerol and glucagon.

Glycerol

Lactate DRUG

Subjects will receive an infusion of lactate and glucagon.

Lactate

Glucose DRUG

Subjects will receive an infusion of glucose and glucagon.

Glucose

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-70 years.
• The subject is otherwise in general good health, based on medical history and physical examination.
• No evidence of T2D or prediabetes as indicated by the American Diabetes Association (ADA), i.e., HbA1c \< 5.7%, fasting glucose \< 100 mg/dL, or use of glucose-lowering medications.
• Body mass index (BMI) ≤ 24.9 kg/m2.
• No evidence of T2D or prediabetes as per ADA criteria.
• ≤ BMI ≤ 45.0 kg/m2.
• Evidence of T2D as indicated by ADA criteria.
• % ≤ HbA1c ≤ 8.0%.
• ≤ BMI ≤ 45.0 kg/m2.

You may not qualify if:

• Chronic medical conditions that may affect glucose metabolism, including active malignancy, tobacco use, HIV infection, kidney failure, liver dysfunction, alcoholism, pancreatitis, active viral/bacterial infection, current pregnancy/lactation, anemia, severe cardiac or respiratory failure, and uncontrolled hyperlipidemia (total cholesterol ≥ 260 mg/dL or triglycerides ≥400 mg/dL).
• Current medical therapy that affects glucose metabolism such as glucocorticoid, antipsychotic, or oral contraceptive pills.
• Type 1 diabetes mellitus diagnosis and/or history of diabetic ketoacidosis.
• Use of weekly glucagon-like peptide-1 (GLP-1) receptor agonist therapy.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Diabetes Mellitus

Interventions

Glycerol; Lactic Acid; Glucose

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triose Sugar Alcohols; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Lactates; Hydroxy Acids; Carboxylic Acids; Hexoses; Monosaccharides; Sugars

Study Officials

• Ankit Shah, MD

  Rutgers Robert Wood Johnson Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ankit Shah, MD

CONTACT

7322356337; ashah386@rwjms.rutgers.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 24, 2025
• First Posted: May 2, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2030
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share