Change of Fructose to Fat in South Asians

• Sponsor: The Rogosin Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01562782
• Collaborator: Weill Medical College of Cornell University (Other)
• Enrollment: 39
• Locations: 2
• Arms: 2
• Actual Duration (Months): 18.3
• Patients Per Site: 19.5
• Patients Per Site Per Month: 1.1

Study Details

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	N/A

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
• 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: Apr 2, 2012
• Actual Primary Completion Date: Oct 10, 2013
• Actual Study Completion Date: Oct 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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [1 hour]

   A comparison of peak levels of glucose at 1 hour. Glucose is expected to increase after ingestion of glucose/fructose.

Eligibility Criteria

Criteria

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

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

	Site	City	State	Country	Postal Code
1	The Rogosin Institute	New York	New York	United States	10065
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: The Rogosin Institute
• ClinicalTrials.gov Identifier: NCT01562782
• Other Study ID Numbers: 1110011995
• First Posted: Mar 26, 2012
• Last Update Posted: Jul 19, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• 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

Study Results

Participant Flow

Recruitment Details	Between 4/2012 and 10/2013 fifteen South Asians and 15 Caucasians were studied as outpatients at the Weill Cornell Medical College Clinical and Translational Science Center (CTSC).
Pre-assignment Detail	At the CTSC clinic, consented volunteers had their medical history reviewed and a physical exam performed. A fasting blood sample was obtained to screen for lipid and biochemical abnormalities, thyroid and liver disease, anemia, pregnancy and diabetes/glucose intolerance.

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Control group: The arm is an oral sugar challenge with blood sampling over 4 hours. 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.	South Asian group: The arm is an oral sugar challenge with blood sampling over 4 hours. 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.
Period Title: Overall Study
STARTED	19	20
COMPLETED	15	15
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Caucasian	South Asians	Total
Arm/Group Description	Control group: The arm is an oral sugar challenge with blood sampling over 4 hours. 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.	Experimental group: The arm is an oral sugar challenge with blood sampling over 4 hours. 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.	Total of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	15 100%	30 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28 (3)	26 (5)	27 (4)
Sex: Female, Male (Count of Participants)
Female	8 53.3%	8 53.3%	16 53.3%
Male	7 46.7%	7 46.7%	14 46.7%
Region of Enrollment (participants) [Number]
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Fold Change in Plasma Very Low Density Lipoprotein (VLDL) Triglyceride Palmitate
Description	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.
Time Frame	4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [fold change]	1.24 (0.87)	1.85 (0.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments	The equivalence test was used to compare the fold change in plasma VLDL triglyceride palmitate in Caucasians and South Asians.
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups in the primary outcome- the mean fold change in plasma VLDL triglyceride palmitate, 0-4 hours. A power calculation was based on data obtained in 15 overweight subjects. Assuming a mean absolute difference of 2.7 in South Asians and 1.0 in Caucasians and a standard deviation of 2.0 for both, group sample sizes of 16 and 16 were expected to achieve 80% power to detect a difference of 1.7 using a 2-sided Mann-Whitney test.
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.61
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Fold Changes in VLDL Triglycerides in South Asians and Caucasians
Description	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.
Time Frame	4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [fold change]	1.05 (0.56)	1.44 (0.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments	The equivalence test was used to compare 1) the fold change in triglycerides in South Asians and Caucasians and 2) the fold change in VLDL triglycerides in South Asians and Caucasians.
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Peak Glucose Levels in 2 Study Groups
Description	A comparison of peak levels of glucose at one hour. Glucose is expected to increase after ingestion of glucose/fructose.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [mmol/L]	5.16 (1.83)	5.61 (1.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments	The equivalence test is used to compare levels after the sugar beverage of 1) glucose at 1 hour 2) lactate at 1 hour 3) NEFA at 2 hours in South Asians vs Caucasians.
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Peak Insulin Levels in 2 Study Groups
Description	A comparison of the mean peak insulin level at one hour in each group. Insulin is expected to increase after ingestion of glucose/fructose.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [IU/L]	93 (78)	111 (45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Peak Gastric Inhibitory Protein (GIP) Levels in the 2 Study Groups
Description	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.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [ng/L]	277 (90)	274 (99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Correlations Between Fold Change in VLDL TG Palmitate and Other Biomarkers of Carbohydrate and Fat Metabolism
Description	Correlations between fold change in VLDL TG palmitate at 4 hours with other biomarkers of carbohydrate and fat metabolism in each study group.
Time Frame	4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
fold change VLDL TG palmitate 4h: VLDL TG 0h	0.1137	0.0127
fold change VLDL TG palmita 4h:fold change VLDL TG	0.3339	0.3149
fold change VLDL TG palmitate 4h:total TG 0h	0.2320	0.0359
fold change VLDL TG palmitat: fold change total TG	0.3340	0.3290
fold change VLDL TG palmitate 4h:cholesterol 0h	-0.0327	-0.3910
fold change VLDL TG palmitat 4h:HDL cholesterol 0h	0.0883	-0.3743
fold change VLDL TG palmita 4h:apolipoprotein B 0h	0.0587	-0.1459
fold change VDLD TG palm 4h:LDL particle number 0h	-0.0045	-0.0849
fold change VDLD TG palmitate 4h:LDL size 0h	0.1508	0.0359
fold change VLDL TG palmitate 4h:glucose 0h	-0.2444	0.0188
fold change VDLD TG palmitate 4h:glucose AUC	0.2677	-0.1569
fold change VDLD TG palmitate 4h:insulin 0h	-0.2778	-0.1151
fold change VDLD TG palmitate 4h:insulin AUC	0.1886	-0.0070
fold change VDLD TG palmitate 4h:NEFA 0h	0.0241	-0.5689
fold change VDLD TG palmitate 4h:NEFA nadir 2h	0.1319	-0.6151
fold change VDLD TG palmitate 4h:lactate 0h	0.1082	0.4382
fold change VDLD TG palmitate 4h:lactate peak 1h	0.1393	-0.1953
fold change VDLD TG palmitate 4h:GIP 0h	-0.3237	-0.2644
fold change VDLD TG palmitate 4h:GIP peak 2h	0.2889	-0.0453
fold change VDLD TG palmitate 4h:HOMA-R 0h	-0.2892	-0.1104
fold change VDLD TG palmitate 4h:HOMA-B% 0h	-0.2347	0.2959
fold change VDLD TG palmitate 4h:hsCRP 0h	0.0278	0.2463

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments	The equivalence test was used to analyze the relationship between the primary outcome, fold change in VLDL TG palmitate, and the listed levels of biomarkers of carbohydrate and fat metabolism. The correlation analysis was performed on data from each study group separately.
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Pearson or Spearman's rank test
	Comments

7. Secondary Outcome

Title	Fold Changes in Triglycerides in 2 Study Groups
Description	1) A comparison of the fold changes in total triglycerides (TG) in the 2 study groups between 0 and 4 hours.
Time Frame	4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [fold change]	1.05 (0.56)	1.43 (0.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Peak Lactate Levels in 2 Study Groups
Description	A comparison of peak levels of lactate (at one hour). Lactate is expected to increase after ingestion of glucose/fructose.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [mmol/L]	3.43 (1.15)	3.91 (0.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	Nadir Non-esterified Fatty Acids (NEFA) Levels in 2 Study Groups
Description	A comparison of the nadir level of non-esterified fatty acids (NEFA at 2 hours). NEFA are expected to decrease.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [mmol/L]	0.09 (0.05)	0.09 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	Peak Glucose in 2 Study Groups
Description	A comparison of peak levels of glucose at 1 hour. Glucose is expected to increase after ingestion of glucose/fructose.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caucasians	South Asians
Arm/Group Description	Caucasian control group	South Asian experimental group
Measure Participants	15	15
Mean (Standard Deviation) [mmol/L]	5.16 (1.83)	5.61 (1.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caucasians, South Asians
	Comments
	Type of Statistical Test	Equivalence
	Comments	A P value <0.05 was used to determine no equivalence between groups.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	4 hours per participant.
Arm/Group Title	Caucasians		South Asians
Arm/Group Description	Caucasian control group		South Asian experimental group
All Cause Mortality
	Caucasians		South Asians
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Caucasians		South Asians
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Caucasians		South Asians
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		1/15 (6.7%)
Gastrointestinal disorders
nausea	0/15 (0%)	0	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.