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SGLTi, Hepatic Glucose Production and Ketogenesis

Description

In this study, we will test the hypothesis that distinct mechanisms account for the SGLT2i-induced stimulation of ketogenesis and lipolysis versus endogenous (hepatic) glucose production in patients with type 2 diabetes (T2D) and type 1 diabetes (T1D), and that the increases in ketone production and lipolysis can be prevented by concomitant administration of the thiazolidinedione pioglitazone. We will conduct five distinct experiments to test this hypothesis in patients with T2D and T1D. MAIN STUDY: To examine the effect of empagliflozin versus empagliflozin/pancreatic clamp on EGP (6,6, D2-glucose), gluconeogenesis (D2O), lipolysis (U-2H-glycerol), ketogenesis (13C-palmitate conversion to 3-betahydroxybuyrate), and norepinephrine turnover (3H-NE) in type 2 diabetes subjects.

Conditions

Type 2 Diabetes
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Related Conditions:

Type 2 Diabetes

Study Overview

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Study Details

Study overview

In this study, we will test the hypothesis that distinct mechanisms account for the SGLT2i-induced stimulation of ketogenesis and lipolysis versus endogenous (hepatic) glucose production in patients with type 2 diabetes (T2D) and type 1 diabetes (T1D), and that the increases in ketone production and lipolysis can be prevented by concomitant administration of the thiazolidinedione pioglitazone. We will conduct five distinct experiments to test this hypothesis in patients with T2D and T1D. MAIN STUDY: To examine the effect of empagliflozin versus empagliflozin/pancreatic clamp on EGP (6,6, D2-glucose), gluconeogenesis (D2O), lipolysis (U-2H-glycerol), ketogenesis (13C-palmitate conversion to 3-betahydroxybuyrate), and norepinephrine turnover (3H-NE) in type 2 diabetes subjects.

Protocol l: SGLT2 Inhibitors, Ketogenesis, and Ketoacidosis

SGLTi, Hepatic Glucose Production and Ketogenesis

Condition
Type 2 Diabetes
Intervention / Treatment

-

Contacts and Locations

San Antonio

Texas Diabetes Institute/UH, San Antonio, Texas, United States, 78229-3900

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Ages 30-75 years
  • * Body Mass Index (BMI) 21-45 kg/m2
  • * Hemoglobin A1C (HbA1c) = 7.0-11%
  • * Estimated glomerular filtration rate (eGFR) \> 60 ml/min/1.73m2
  • * Blood Pressure (BP) \< 160/90 mmHg
  • * Participants must be in general good health based on medical history, physical exam, screening blood chemistries, complete blood chemistry (CBC), thyroid stimulating hormone/thyroxine (TSH/T4), electrocardiogram (EKG), and urinalysis
  • * Stable body weight (±1.5 kg) over the last 3 months and must not participate in an excessively heavy exercise program
  • * Patients treated with diet, sulfonylurea (SU), metformin (MET), or SU/MET
  • * Statin therapy is permissible if the dose has been stable for at least 3 months
  • * Patients treated with Glucagon-like peptide 1 receptor agonists (GLP-1 RA), Dipeptidyl Peptidase IV inhibitors (DPP-4i), Thiazolidinediones (TZD), or insulin are excluded
  • * Patients taking medications (other than SU/MET) known to affect glucose metabolism are excluded
  • * Subjects with evidence of proliferative retinopathy or eGFR \< 60 are excluded
  • * Women of childbearing potential are excluded unless they are taking/using appropriate contractive medications/devices

Ages Eligible for Study

30 Years to 75 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

The University of Texas Health Science Center at San Antonio,

Ralph DeFronzo, MD, PRINCIPAL_INVESTIGATOR, University of Texas Health Science Center San Antonio

Study Record Dates

2027-06-30