Fructose-induced Hepatic De Novo Lipogenesis in Adolescents With Obesity

Adolescent Obesity Clinical Trial

Official title: Fructose-induced Hepatic De Novo Lipogenesis in Adolescents With Obesity

Status Terminated

Clinical Trial Summary

In the U.S., dietary fructose has increased in parallel with the increase in obesity and may promote the development of diabetes and other chronic diseases. The largest source of dietary fructose is sweetened beverages that are consumed by adolescents more than any other age group.

This protocol will compare the rates of hepatic de novo lipogenesis (DNL), a process in the liver that changes sugar into fat, in two groups of obese adolescents - one with prediabetes and the other, metabolically healthy. Blood will be sampled before and hourly for 3 hours after the consumption of a fructose-containing beverage. We hypothesize that the pre-diabetic group will show greater DNL in response to fructose. This would support other evidence that increased fructose-induced hepatic DNL is an early mechanism linking dietary sugar to the adverse metabolic sequelae of obesity, including diabetes, fatty liver, dyslipidemia and coronary disease.

Clinical Trial Description

Hypothesis: Hepatic DNL in response to the ingestion of fructose:glucose 1:1 is significantly greater in adolescents with obesity and prediabetes compared to adolescents with obesity who are metabolically healthy.

Thirty obese adolescents, ages 12-21 years, will be recruited to each of two groups: 1) prediabetes (n=15) and 2) metabolically healthy (n=15). An attempt will be made to achieve similar age, sex and BMI distributions in the two groups.

Visit 1- Screening: Eligible subjects will be enrolled after Informed consent/assent are obtained by a physician investigator. The medical history will be reviewed and a physical exam performed, including an assessment of pubertal status. Blood will be sampled after at least a 12 hour fast (except water) for complete blood count, serum glutamate pyruvate, glucose, HbA1C, and lipid panel, if not previously documented in the medical record within three months of the screening visit. These tests may be done without fasting, but if the glucose or lipid results are not normal, these two tests must be repeated after fasting.

Visit 2 - Sugar Challenge Test with Blood Sampling: Within three months of the screening visit, eligible participants will return after at least a 12 hour fast (except water). General health, family history and recent diet will be reviewed. The height, weight, waist circumference at the umbilicus, and blood pressure will be recorded. A urine sample will be obtained for microalbuminuria. After placement of an intravenous catheter and withdrawal of the baseline blood samples, participants will drink a sweet beverage prepared by a dietician (fructose:glucose 1:1, 3g/kg, in water). Blood sampling will continue every hour for three hours( ~12 mL per time point).

Percent body fat will be measured by bioimpedance. The percent body fat will be calculated by computer software with prediction equations validated in the pediatric and adult age ranges.

Plasma samples will be obtained at 4 time points (0, 1, 2 and 3 hours), the fatty acid composition of plasma very low density lipoprotein triglyceride (VLDL TG), including %palmitate (16:0), will be measured. A lipid panel and VLDL triglycerides and apolipoprotein B levels will also be measured at each time point. Other assays to be performed include insulin and and glucose, HbA1C and high sensitivity C reactive protein (hsCRP, a marker of inflammation). The urine sample will be assayed for microalbuminuria (albumin/creatinine >30 mg/g).

An interim analysis of the primary endpoint (increase in VLDL TG %16:0) will be performed in the first three subjects of each group to determine whether the dose of sugar and sampling duration of 3 hours are sufficient to produce a measurable increase in VLDL TG %16:0. ;

Related Conditions & MeSH terms

• Adolescent Obesity
• Obesity
• Pediatric Obesity

• NCT number: NCT03567837
• Study type: Interventional
• Source: The Rogosin Institute
• Status: Terminated
• Phase: N/A
• Start date: August 13, 2018
• Completion date: June 4, 2019