Change of Fructose to Fat in South Asians

• ClinicalTrials.gov Identifier: NCT01562782
• Recruitment Status: Completed
• First Posted: March 26, 2012
• Results First Posted: July 19, 2019
• Last Update Posted: July 19, 2019
• Sponsor: The Rogosin Institute
• Collaborator: Weill Medical College of Cornell University
• Information provided by (Responsible Party): The Rogosin Institute

Study Description

Brief Summary:

The purpose of this study is to determine whether hepatic de novo lipogenesis (DNL) in response to the ingestion of a mixture of glucose and fructose is greater in South Asians compared to controls (Caucasians).

Condition or disease	Intervention/treatment	Phase
Elevated Triglycerides; Diabetes; Cardiovascular Disease; Dyslipidemia	Other: Fructose + Glucose Beverage	Not Applicable

Detailed Description:

South Asians, who originate from the Indian subcontinent and make up one-fifth of the world's population, are among the highest number who suffer from heart disease and diabetes. The results of many research studies suggest that genes play a role in developing heart disease and diabetes that is made worse by the diet in the United States. Fructose is a sugar widely used in the American diet, and when consumed, it is taken up by the liver and changed into fats through a process called de novo lipogenesis (DNL). The current study will compare this change into fats in the liver between South Asians and Caucasians. The participants will be screened on the initial visit, and on the second visit, the DNL response will be measured in the blood over four hours after drinking one sweetened beverage, containing half glucose, half fructose, similar to a soft drink. We expect that DNL in response to fructose intake is higher in South Asians when compared to Caucasians and may partially explain why South Asians have earlier heart disease and diabetes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Fructose-induced Hepatic De Novo Lipogenesis in South Asians
• Actual Study Start Date: April 2, 2012
• Actual Primary Completion Date: October 10, 2013
• Actual Study Completion Date: October 10, 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: South Asians; Participants in this group have only South Asian heritage. The intervention is Fructose + Glucose Beverage.	Other: Fructose + Glucose Beverage; Consumption of a sweet beverage (Fructose:Glucose 1:1, 3g/kg) over 1/2 hour. Blood sampling will occur before and after consumption of beverage.
Active Comparator: Caucasians; Participants in this group have only Caucasian heritage. The intervention is Fructose + Glucose Beverage.	Other: Fructose + Glucose Beverage; Consumption of a sweet beverage (Fructose:Glucose 1:1, 3g/kg) over 1/2 hour. Blood sampling will occur before and after consumption of beverage.

Outcome Measures

Primary Outcome Measures :

1. Fold Change in Plasma Very Low Density Lipoprotein (VLDL) Triglyceride Palmitate [ Time Frame: 4 hours ]
   Fold change in plasma very low density lipoprotein (VLDL) triglyceride palmitate between South Asians and Caucasians from baseline to 4 hours after an oral challenge of fructose:glucose, 1:1.

Secondary Outcome Measures :

1. Fold Changes in VLDL Triglycerides in South Asians and Caucasians [ Time Frame: 4 hours ]
   1) A comparison of the fold changes in very low density lipoprotein triglycerides (VLDL TG)in the 2 study groups between 0 and 4 hours.
2. Peak Glucose Levels in 2 Study Groups [ Time Frame: 1 hour ]
   A comparison of peak levels of glucose at one hour. Glucose is expected to increase after ingestion of glucose/fructose.
3. Peak Insulin Levels in 2 Study Groups [ Time Frame: 1 hour ]
   A comparison of the mean peak insulin level at one hour in each group. Insulin is expected to increase after ingestion of glucose/fructose.
4. Peak Gastric Inhibitory Protein (GIP) Levels in the 2 Study Groups [ Time Frame: 2 hours ]
   A comparison of the mean peak gastric inhibitory protein (GIP) at 2 hours in each group. GIP is expected to increase after ingestion of glucose/fructose.
5. Correlations Between Fold Change in VLDL TG Palmitate and Other Biomarkers of Carbohydrate and Fat Metabolism [ Time Frame: 4 hours ]
   Correlations between fold change in VLDL TG palmitate at 4 hours with other biomarkers of carbohydrate and fat metabolism in each study group.
6. Fold Changes in Triglycerides in 2 Study Groups [ Time Frame: 4 hours ]
   1) A comparison of the fold changes in total triglycerides (TG) in the 2 study groups between 0 and 4 hours.
7. Peak Lactate Levels in 2 Study Groups [ Time Frame: 1 hour ]
   A comparison of peak levels of lactate (at one hour). Lactate is expected to increase after ingestion of glucose/fructose.
8. Nadir Non-esterified Fatty Acids (NEFA) Levels in 2 Study Groups [ Time Frame: 2 hours ]
   A comparison of the nadir level of non-esterified fatty acids (NEFA at 2 hours). NEFA are expected to decrease.
9. Peak Glucose in 2 Study Groups [ Time Frame: 1 hour ]
   A comparison of peak levels of glucose at 1 hour. Glucose is expected to increase after ingestion of glucose/fructose.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Males and females, 18-35 years of age.
• South Asian or Caucasian descent through self-identification (South Asians are to have both biological parents with ancestry from India, Pakistan, Sri Lanka, Nepal and Bangladesh and no known non-South Asian ancestry in parents; Caucasians are to have both biological parents who self-identify as Caucasian and no known non-Caucasian ancestry in parents).
• Body mass index (BMI) 18.0-24.9 kg/m2 with no history of obesity.
• Fasting glucose <100 mg/dL, 2h glucose oral glucose tolerance test (OGTT) < 140 mg/dL.
• triglycerides (TG) <200 mg/dL, HDL cholesterol (HDL-C) >30 mg/dL, LDL cholesterol (LDL-C) <160 mg/dL.
• Willing and able to stop fish oil, fiber supplement, other non-prescribed vitamins/supplements for 1 week prior to visit #2 until completion of study.
• Willing to not drink alcohol for 24-hours before visit #2.
• Willing and able to provide informed consent.

Exclusion Criteria:

• History of diabetes or other endocrine disorder, hepatitis or other liver disorder, HIV, or autoimmune disease.
• Medication(s) known to affect lipids, including hormonal contraceptives.
• Recent acute illness
• Gastrointestinal disease resulting in significant gastrointestinal dysfunction or malabsorption.
• Cigarette smoking
• History of ethanol abuse (current intake >2 drinks/day) or illicit drugs.
• History of severe psychiatric illness
• If female, pregnant or breastfeeding
• Participation in an investigational drug study within one month of screening.
• Unusual diet or extreme level of physical activity
• Have any other condition, which in the opinion of the investigator, should prohibit the participation in the study

Contacts and Locations

Locations

United States, New York

The Rogosin Institute

New York, New York, United States, 10065

Weill Cornell Medical College Clinical and Translational Science Center (CTSC)

New York, New York, United States, 10065

Sponsors and Collaborators

The Rogosin Institute

Weill Medical College of Cornell University

Investigators

• Principal Investigator: Lisa Hudgins, MD; The Rogosin Institute

More Information

• Responsible Party: The Rogosin Institute
• ClinicalTrials.gov Identifier: NCT01562782
• Other Study ID Numbers: 1110011995
• First Posted: March 26, 2012
• Results First Posted: July 19, 2019
• Last Update Posted: July 19, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The Rogosin Institute:

Elevated triglycerides; Diabetes Mellitus; Dyslipidemia; Lipid Metabolic Disorders; Body Weight

Additional relevant MeSH terms:

Cardiovascular Diseases; Dyslipidemias; Hypertriglyceridemia; Lipid Metabolism Disorders; Metabolic Diseases; Hyperlipidemias