Clinical trial

Lactate and Glycerol Contribution to Gluconeogenesis

Opening soon · Not applicable · 0 countries · Registry ID NCT06955130

Opening soonNot applicableInterventional

What this study is about

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.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age40 Years to 70 Years
SexAll
Healthy volunteersAccepted
ConditionType 2 Diabetes, Obesity, Healthy

Full registry criteria

Inclusion Criteria for All Subjects 1. Age 40-70 years. 2. The subject is otherwise in general good health, based on medical history and physical examination. Inclusion Criteria for Metabolically Healthy Subjects without Obesity 1. 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. 2. Body mass index (BMI) ≤ 24.9 kg/m2. Inclusion Criteria for Metabolically Healthy Subjects with Obesity 1. No evidence of T2D or prediabetes as per ADA criteria. 2. 30.0 ≤ BMI ≤ 45.0 kg/m2. Inclusion Criteria for T2D Subjects 1. Evidence of T2D as indicated by ADA criteria. 2. 6.5% ≤ HbA1c ≤ 8.0%. 3. 30.0 ≤ BMI ≤ 45.0 kg/m2. Exclusion Criteria for All Subjects 1. 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). 2. Current medical therapy that affects glucose metabolism such as glucocorticoid, antipsychotic, or oral contraceptive pills. 3. Type 1 diabetes mellitus diagnosis and/or history of diabetic ketoacidosis. 4. Use of weekly glucagon-like peptide-1 (GLP-1) receptor agonist therapy.

Treatments and study arms

Glycerol

Drug

Subjects will receive an infusion of glycerol and glucagon.

Lactate

Drug

Subjects will receive an infusion of lactate and glucagon.

Glucose

Drug

Subjects will receive an infusion of glucose and glucagon.

Primary outcomes

Carbon Contribution to Glucose Production8 hours

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

Study locations

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No public site location was included in this record. Check the original registry for updates.