Glycemic Index and Brain Function

• Subjective Hunger Rating [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Glucose Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Insulin Level [ Time Frame: Every 30 minutes for 5 hours ] [ Designated as safety issue: No ]
• Blood Glucagon Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Growth Hormone Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Epinephrine Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Fatty Acids Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
  measuring metabolite profiles

• Subjective Hunger Rating [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Glucose Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Insulin Level [ Time Frame: Every 30 minutes for 5 hours ] [ Designated as safety issue: No ]
• Blood Glucagon Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Growth Hormone Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Epinephrine Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]
• Blood Fatty Acids Level [ Time Frame: Every 30 minutes for 5 hours. ] [ Designated as safety issue: No ]

The investigators propose examine the effects of the dietary factor glycemic index (GI) on brain areas that control food intake and hunger. This knowledge could help design dietary approaches that decrease hunger, and thus promote new weight loss strategies.

Most individuals have great difficulty following reduced calorie diets because they experience increased hunger. This process is regulated by specific brain areas. Though many psychological and environmental factors are involved, physiological effects of diet may have a significant impact. The postprandial rise in blood glucose, quantified by the glycemic index (GI), is of particular interest. High GI meals elicit hormonal events that limit availability of metabolic fuels, causing hunger and overeating, especially in people with high insulin secretion.

Our aim is to examine how postprandial changes after high versus low GI meals affect hunger and brain function in areas of intake control. Specifically, we speculate that obese individuals will demonstrate functional changes in brain areas of intake control and increased hunger after a high versus low GI meal.

We will recruit obese, young adults and quantify their insulin secretion during a 2-hour oral glucose tolerance test. A brief practice MRI session will serve to familiarize the subjects with the scanning process. During the two test sessions, standardized test meals with high versus low GI will be given in a randomized, blinded cross-over design. Serial blood levels of hormones, metabolic fuels, and metabolites will be correlated with perceived hunger, and a perfusion MRI scan will be performed to assess brain activation during the late postprandial phase, at the nadir of blood sugar and insulin levels (4 hours postprandial).

This work will inform an integrated physiological model relating peripheral postprandial changes to brain function and hunger. In addition, findings may provide evidence of a novel diet-phenotype, in which baseline clinical characteristics can be used to predict which weight loss diet will work best for a specific individual. Metabolite profiling might shed light on the mechanisms linking diet composition to brain function, and provide feasible clinical markers of the identified phenotype to facilitate translation into practice.

• Other: Low GI
  Subjects will be instructed to consume a liquid test meal with a low GI over 5 minutes after baseline laboratory evaluations. The low and high GI meal contain similar amounts of milk, oil, dried egg whites, equal, and vanilla extract. The low GI meal corn-starch as a carbohydrate. Both meals have similar macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. The high vs. low GI meals have a predicted difference in GI of 90 vs. 40, and consistent with this prediction, a pilot study in obese young adults found a 2.2-fold difference in glycemic response (p<0.001). The test meals will provide 25% of individual daily energy requirements.
• Other: High GI
  Subjects will be instructed to consume a liquid test meal with a high GI over 5 minutes after baseline laboratory evaluations. The low and high GI meal contain similar amounts of milk, oil, dried egg whites, equal, and vanilla extract. The high GI meal contains corn-syrup as a carbohydrate. Both meals have similar macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. The high vs. low GI meals have a predicted difference in GI of 90 vs. 40, and consistent with this prediction, a pilot study in obese young adults found a 2.2-fold difference in glycemic response (p<0.001). The test meals will provide 25% of individual daily energy requirements.

• Active Comparator: Low GI
  Intervention: Other: Low GI
• Experimental: High GI
  Intervention: Other: High GI

Inclusion criteria

1. Males age 18 to 35 years
2. BMI less than or equal to 25 for age and gender

Exclusion criteria

1. weight > 300 lbs
2. largest body circumference > 144cm
3. body shape incompatible with MRI scanner or equipment
4. MRI exclusion criteria
5. large fluctuations in body weight (5% over preceding 6 months, 2.5% during the study)
6. known medical problems that may affect metabolism or hormones
7. diabetes mellitus (fasting plasma glucose ≥126 mg/dL)
8. other abnormal laboratory screening tests
9. taking any medications or dietary supplements that might affect body weight, appetite, or energy expenditure
10. smoking or illicit substance abuse
11. high levels of physical activity (>30 minutes per day, > 4days per week)
12. currently following a weight loss diet
13. allergies or intolerance to eggs, vanilla extract, equal, canola oil, milk, cornstarch, corn syrup

• Children's Hospital Boston
• Brigham and Women's Hospital