Visceral Adiposity and Diabetes: Translating Form to Function Using Imaging

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2018-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study is a clinical study to investigate the gluconeogenesis pathway related to visceral adipose tissue (VAT) in obese individuals without type 2 diabetes and the effects of empagliflozin (EMPA) on glucose homeostasis in viscerally-obese individuals using functional studies of glycerol metabolism in hepatic gluconeogenesis using a well-validated nuclear magnetic resonance (NMR) spectroscopy platform.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Avoidance of Insulin-induced Lipohypertophy in People With Diabetes Using Ultrasound Scanning Within Diabetes Clinics

NCT06782568

Type 1 Diabetes (T1D) Type 2 Diabetes, Insulin Requiring

NOT_YET_RECRUITING NA

Effects of Empagliflozin on Liver Fat Content, Energy Metabolism and Body Composition in Patients With Type 2 Diabetes

NCT02637973

Type 2 Diabetes Non-alcoholic Fatty Liver Disease

COMPLETED PHASE4

Efficacy of GLP-1 Receptor Agonists in Treating Upper and Lower Extremity Lymphedema

NCT07012642

Lymphedema

RECRUITING EARLY_PHASE1

Paradoxical Stimulation of Hepatic Glucose Production With Dapagliflozin

NCT02984644

Type II; Diabetes

COMPLETED PHASE3

Empagliflozin and Hepatic Glucose Metabolism

NCT03193684

Hepatic Glucose Metabolism

COMPLETED PHASE4

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Diabetes mellitus type II is the consequence of insulin resistance and pancreatic beta cell failure resulting from a variety of metabolic insults, one of which is excess body adiposity/obesity. In the diabetic individual, hepatic gluconeogenesis may go uninhibited due to failure of the body's normal feedback mechanisms to appropriately incorporate glucose into cells via insulin signaling, leading to excess gluconeogenesis and hyperglycemia. The substrate for this excess glucose derives from multiple sources in the liver including dietary glycerol, adipose-derived glycerol from lipolysis, and substrates from the citric acid cycle. In the normal state, lipolysis is maintained at a steady state in equilibrium between stored dietary triglycerides and free fatty acids. However, in situations of triglyceride excess (e.g. in the obese state), lipolysis may become overactive resulting in increased free fatty acids and adipose-derived glycerol. This excess glycerol drives hepatic gluconeogenesis and is incorporated into glucose and released into the blood, leading to hyperglycemia, and ultimately diabetes and its clinical sequelae.

A popular hypothesis linking visceral fat with excess gluconeogenesis is delivery of glycerol arising from mesenteric triglyceride turnover directly into the portal circulation and to the liver. Glycerol is a primary substrate for gluconeogenesis in the liver. Under normal conditions, hepatic gluconeogenesis begins from glycerol ingested in the diet which is converted to glycerol-3-phosphate and subsequently dihydroxyacetone phosphate (DHAP) in the liver. DHAP is converted to fructose-1,6-bisphosphate which undergoes a series of reactions to become a single 6-carbon glucose molecule. Adipocytes contribute glycerol to hepatic gluconeogenesis through lipolysis of triglyceride stores. Although glycerol-gluconeogenesis has been extensively studied in animals, the traditional reliance on radioactive tracers makes translation to humans difficult for many reasons. We aim to use new techniques to explore the mechanisms behind altered glucose metabolism related to excess visceral adiposity in obese adults by quantifying the relative contributions of varying substrates to liver-derived glucose. One such method uses 13C3 labeled glycerol to trace the incorporation of glycerol from dietary sources to hepatic gluconeogenesis. This technology utilizes nuclear magnetic resonance (NMR) spectroscopy, a technique that does not require ionizing radiation and has been extensively validated, to analyze the NMR spectra of plasma glucose and quantify the "percent enrichment" of the circulating glucose molecules with labeled glycerol. In turn, differences in enrichment reflect variability in hepatic glucose metabolism as it relates to the contribution of glycerol from visceral adipose tissue to gluconeogenesis.

The rationale of this project is to utilize existing technology to investigate the impact of excess visceral adiposity on glycerol metabolism in hepatic gluconeogenesis in obese adults without diabetes and to explore the effects of treatment with EMPA on visceral adiposity related glucose homeostasis.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Obesity, Visceral

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Empagliflozin

Empagliflozin 10 mg by mouth daily for 3 months.

Group Type EXPERIMENTAL

[U-13C3] glycerol

Intervention Type DRUG

Ingestion of \[U-13C3\] glycerol based on human's body weight such as (50 mg/kg body weight).

Empagliflozin

Intervention Type DRUG

Active drug

Placebo

Placebo one tablet daily for 3 months

Group Type PLACEBO_COMPARATOR

[U-13C3] glycerol

Intervention Type DRUG

Ingestion of \[U-13C3\] glycerol based on human's body weight such as (50 mg/kg body weight).

Placebo (for Empagliflozin)

Intervention Type DRUG

Placebo tablet manufactured to mimic EMPA 10 mg tablet.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

[U-13C3] glycerol

Ingestion of \[U-13C3\] glycerol based on human's body weight such as (50 mg/kg body weight).

Intervention Type DRUG

Empagliflozin

Active drug

Intervention Type DRUG

Placebo (for Empagliflozin)

Placebo tablet manufactured to mimic EMPA 10 mg tablet.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Glycerine Glycerin EMPA Jardiace Placebo Sugar pill

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Obese, defined as BMI ≥ 30 kg/m2, at both time of abdominal fat imaging and at study entry.
* Ages 30-65
* No prevalent diagnosis of type 2 diabetes mellitus, either at the time of abdominal fat imaging or at study entry.
* Previous abdominal fat quantification by magnetic resonance imaging in the Dallas Heart Study or possible neck-to-knee MRI for VAT measurement may be performed.

Exclusion Criteria

* Pregnant or breastfeeding
* Incarcerated
* Chronic kidney or liver disease
* History of frequent (\>2/year) urinary tract infections
* Non-obese either at time of abdominal fat imaging or at present.
* Greater than 10% change in body weight (kg) between time of abdominal fat imaging and present.
* Has donated blood within last 6 weeks
* Cannot give informed consent, understand the protocol, or tolerate any aspect of the protocol
* If undergoing MRI, persons with metal implants contraindicated for 3Tesla MRI exams will be excluded. Severe claustrophobia will also be assessed prior to an MRI exam.

Minimum Eligible Age

30 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes