Insulin Resistance, Insulin Sensitivity, Pre Diabetes
Conditions
Keywords
Fructose, Glucose, Lipogenesis
Brief summary
This objective of this study is to use sensitive methodology under controlled conditions to investigate the mechanisms by which fructose consumption contributes to excess fatty acid synthesis and elevations in blood glucose levels following consumption of meals containing fructose.
Interventions
OTHERHigh fructose, fructose labeled meal
Liquid meal containing high fructose (16% of energy), labeled with 2-13C fructose
OTHERHigh fructose, pyruvate labeled meal
Liquid meal containing high fructose (16% of energy), labeled with 2-13C pyruvate
OTHERLow fructose, fructose labeled meal
Liquid meals containing low fructose (6% of energy), labeled with 2-13C fructose
OTHERLow fructose, pyruvate labeled meal
Liquid meal containing low fructose (6% of energy), labeled with 2-13C pyruvate
Sponsors
Touro University, California
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body Mass Index 22 to 35 kg/m2 * Prediabetic (HbA1c 5.7% to 6.5%) or hyperinsulinemic (fasting insulin ≥12 µIU/mL) but non-diabetic (fasting glucose \<126mg/dL and HbA1c \< 6.5%) ; or normal control (fasting insulin \<10 µIU/mL, fasting glucose \<100 mg/dL, and HbA1c \< 5.7%)
Exclusion criteria
* Pregnancy or lactation within the past six months * Type 1 or 2 diabetes mellitus * History of liver disease or aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2x the upper limit of normal (ULN); * Fasting triglyceride or total cholesterol levels above 95th percentile for age and sex; * Hemoglobin or hematocrit below the lower limit of normal for sex; * Report of hepatitis or HIV infection; * History of cancer, use of any anti-diabetic medications or hypolipidemic agents in the past six months; * History of surgical procedure for obesity; * Self-reported change in body weight \>5% in the past six months; * History of other conditions known to affect insulin sensitivity and lipid metabolism; * Known intolerance to acetaminophen or components of the liquid test meals.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic fractional de novo lipogenesis in triglyceride rich lipoprotein (TRL) | 6 hours | Measured by the detection of 13C carbons in TRL-palmitate from administered 13C labeled pyruvate or 13C labeled fructose. |
| Rate of appearance of UDP-glucose | 6 hours | An estimate of hepatic glycogen flux measured by administration of D1 galactose and acetaminophen |
| Rate of appearance of blood glucose from gluconeogenesis | 6 hours | Measured by the dilution method of labeled glucose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum triglyceride concentration | 6 hours | Fasting and postprandial serum triglyceride levels |
| Serum glucose concentration | 6 hours | Fasting and postprandial serum triglyceride levels |
| Serum lactate concentration | 6 hours | Fasting and postprandial serum lactate levels |
| Serum insulin concentration | 6 hours | Fasting and postprandial insulin levels |
| Serum free fatty acid concentration | 6 hours | Fasting and postprandial fatty acid levels |
| Enteral (chylomicron) fractional de novo lipogenesis (DNL) | 6 hours | Measured by the detection of 13C carbons in chylomicron-palmitate from administered 13C labeled pyruvate or 13C labeled fructose. |
| Hepatic (VLDL) fractional de novo lipogenesis (DNL) | 6 hours | Measured by the detection of 13C carbons in VLDL-palmitate from administered 13C labeled pyruvate or 13C labeled fructose. |
| Extrasplanchnic fructose | 6 hours | Calculated using total plasma fructose, plasma 2-13C fructose enrichment, and endogenous fructose production |
| Whole body fructose oxidation | 6 hours | Measured by 13C atom % excess in exhaled breath, and VCO2 by indirect calorimetry |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJean-Marc Schwarz, PhD
Touro University, California
Outcome results
None listed