Trial Outcomes & Findings for Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus (NCT NCT02772783)

Results Overview

Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

15 participants

Primary outcome timeframe

4 hrs postprandial

Results posted on

2021-06-18

Participant Flow

Participants were recruited from the Boston Children's Hospital Diabetes Program and via postings in the surrounding medical area.

Participants underwent a 5 hour pre-randomization visit to establish IV insulin requirement for a low GI test meal. Participants were positioned in the MRI scanner for a brief test sequence. Participants were excluded if they were unable to finish these pre-randomization procedures, or if they decided to not continue.

Participant milestones

Participant milestones
Measure	High GI Matched Glucose - Low GI - High GI Matched Insulin In a randomized cross-over design, a nutritional shake with high GI vs low GI was consumed with differential insulin coverage in the following order: 1. High GI meal covered with IV insulin adjusted using a negative feedback algorithm to achieve euglycemia, resulting in hyperinsulinemia (experimental condition A); 1 day. \- 1-week wash-out 2. Low GI meal covered with IV insulin adjusted using a negative feedback algorithm to achieve euglycemia (comparison condition B); 1 day. \- 1-week wash-out 3. High GI meal with IV insulin matching the low GI meal, resulting in hyperglycemia (experimental condition C); 1 day. High and low GI liquid test meals were matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals provided 25% of individual daily energy requirements. Insulin was given intravenously for 5 hours. Glucose levels were measured every 5 minutes for insulin titration.	High GI Matched Insulin - Low GI - High GI Matched Glucose In a randomized cross-over design, a nutritional shake with high GI vs low GI was consumed with differential insulin coverage in the following order: 1. High GI meal with IV insulin matching the low GI meal (as determined during the pre-randomization visit), resulting in hyperglycemia (experimental condition C); 1 day. \- 1-week wash-out 2. Low GI meal covered with IV insulin adjusted using a negative feedback algorithm to achieve euglycemia (comparison condition B); 1 day. \- 1-week wash-out 3. High GI meal covered with IV insulin adjusted using a negative feedback algorithm to achieve euglycemia, resulting in hyperinsulinemia (experimental condition A); 1 day. High and low GI liquid test meals were matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals provided 25% of individual daily energy requirements. Insulin was given intravenously for 5 hours. Glucose levels were measured every 5 minutes for insulin titration.
Experimental Condition 1, 1 Day STARTED	8	7
Experimental Condition 1, 1 Day COMPLETED	8	7
Experimental Condition 1, 1 Day NOT COMPLETED	0	0
Wash-out, 1 Week STARTED	8	7
Wash-out, 1 Week COMPLETED	8	7
Wash-out, 1 Week NOT COMPLETED	0	0
Comparison Condition, 1 Day STARTED	8	7
Comparison Condition, 1 Day COMPLETED	8	7
Comparison Condition, 1 Day NOT COMPLETED	0	0
Experimental Condition 2, 1 Day STARTED	8	7
Experimental Condition 2, 1 Day COMPLETED	8	7
Experimental Condition 2, 1 Day NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=15 Participants In a randomized cross-over design, a nutritional shake with high GI vs low GI was consumed with differential insulin coverage: * High GI meal covered with IV insulin to to achieve euglycemia, resulting in hyperinsulinemia (experimental condition A); 1 day. * 1-week wash-out * Low GI meal covered with IV insulin to achieve euglycemia (comparison condition B); 1 day. * 1-week wash-out * High GI meal with IV insulin matching the low GI meal, resulting in hyperglycemia (experimental condition A); 1 day. The order of experimental conditions A and B was randomized. High and low GI liquid test meals were matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals provided 25% of individual daily energy requirements. Insulin was given intravenously for 5 hours. Glucose levels were measured every 5 minutes for insulin titration. Because all participants completed all interventions, results are presented in aggregate for the entire study group.
Age, Continuous	21 years STANDARD_DEVIATION 1.6 • n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	15 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	15 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	15 Participants n=93 Participants
BMI	21 kg/m^2 STANDARD_DEVIATION 1.4 • n=93 Participants

PRIMARY outcome

Timeframe: 4 hrs postprandial

Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.

Outcome measures

Outcome measures
Measure	High GI With Matched to Low GI Glucose (HGI HI) n=15 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	Low GI (LGI) n=15 Participants After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	High GI With Matched to Low GI Insulin (HGI LI) n=15 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.
Nucleus Accumbens Blood Flow right	1.13 ml/g/min per ml/g/min Standard Error 0.02	1.16 ml/g/min per ml/g/min Standard Error 0.02	1.15 ml/g/min per ml/g/min Standard Error 0.02
Nucleus Accumbens Blood Flow left	1.21 ml/g/min per ml/g/min Standard Error 0.02	1.18 ml/g/min per ml/g/min Standard Error 0.02	1.18 ml/g/min per ml/g/min Standard Error 0.02

SECONDARY outcome

Timeframe: 1 hr postprandial

Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.

Outcome measures

Outcome measures
Measure	High GI With Matched to Low GI Glucose (HGI HI) n=15 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	Low GI (LGI) n=15 Participants After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	High GI With Matched to Low GI Insulin (HGI LI) n=15 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.
Nucleus Accumbens Blood Flow left	1.20 ml/g/min per ml/g/min Standard Error 0.02	1.19 ml/g/min per ml/g/min Standard Error 0.02	1.14 ml/g/min per ml/g/min Standard Error 0.02
Nucleus Accumbens Blood Flow right	1.12 ml/g/min per ml/g/min Standard Error 0.02	1.16 ml/g/min per ml/g/min Standard Error 0.02	1.11 ml/g/min per ml/g/min Standard Error 0.02

SECONDARY outcome

Timeframe: 4 hrs postprandial

Cerebral blood flow was measured by arterial spin labeling (MRI). Grouped MRI data was visually inspected for postprandial differences between conditions. Blood flow from a cluster contracting the conditions in the right dorsal caudate, just lateral to the nucleus accumbent, was extracted, normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.

Outcome measures

Outcome measures
Measure	High GI With Matched to Low GI Glucose (HGI HI) n=15 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	Low GI (LGI) n=15 Participants After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	High GI With Matched to Low GI Insulin (HGI LI) n=15 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.
Blood Flow in Other Brain Areas Involved in Intake Regulation - Dorsal Caudate	0.60 ml/g/min per ml/g/min Standard Error 0.01	0.59 ml/g/min per ml/g/min Standard Error 0.01	0.64 ml/g/min per ml/g/min Standard Error 0.01

SECONDARY outcome

Timeframe: 1 hr postprandial

Cerebral blood flow was measured by arterial spin labeling (MRI). Grouped MRI data was visually inspected for postprandial differences between conditions. Blood flow from a cluster contracting the conditions in the right ventrolateral striatum, just lateral to the nucleus accumbent, was extracted, normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.

Outcome measures

Outcome measures
Measure	High GI With Matched to Low GI Glucose (HGI HI) n=15 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	Low GI (LGI) n=15 Participants After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	High GI With Matched to Low GI Insulin (HGI LI) n=15 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.
Blood Flow in Other Brain Areas Involved in Intake Regulation - Ventrolateral Striatum	0.60 ml/g/min per ml/g/min Standard Error 0.01	0.61 ml/g/min per ml/g/min Standard Error 0.01	0.60 ml/g/min per ml/g/min Standard Error 0.01

SECONDARY outcome

Timeframe: 4 hrs postprandial

Cerebral blood oxygen concentration level was measured by resting state functional MRI (rs-fMRI). Seed based analysis was performed with the seed on the right Nucleus Accumbens. Functional connectivity between Nucleus Accumbens and Hypothalamus was assessed through extraction of temporal correlation measures.

Outcome measures

Outcome measures
Measure	High GI With Matched to Low GI Glucose (HGI HI) n=13 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	Low GI (LGI) n=13 Participants After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	High GI With Matched to Low GI Insulin (HGI LI) n=13 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.
Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation	0.26 unite-less correlation Standard Error 0.08	0.24 unite-less correlation Standard Error 0.08	0.25 unite-less correlation Standard Error 0.08

SECONDARY outcome

Timeframe: 1 hr postprandial

Cerebral blood oxygen concentration level was measured by resting state functional MRI (rs-fMRI). Seed based analysis was performed with the seed on the right Nucleus Accumbens. Functional connectivity between Nucleus Accumbens and Hypothalamus was assessed through extraction of temporal correlation measures. Functional connectivity between Nucleus Accumbens and other brain areas was visually assessed.

Outcome measures

Outcome measures
Measure	High GI With Matched to Low GI Glucose (HGI HI) n=13 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	Low GI (LGI) n=13 Participants After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.	High GI With Matched to Low GI Insulin (HGI LI) n=13 Participants After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention.
Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation	0.36 unite-less correlation Standard Error 0.09	0.15 unite-less correlation Standard Error 0.09	0.15 unite-less correlation Standard Error 0.09

Adverse Events

High GI With Matched to Low GI Glucose (HGI HI)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Low GI (LGI)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

High GI With Matched to Low GI Insulin (HGI LI)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	High GI With Matched to Low GI Glucose (HGI HI) n=15 participants at risk After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia.	Low GI (LGI) n=15 participants at risk After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia.	High GI With Matched to Low GI Insulin (HGI LI) n=15 participants at risk After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit.
Cardiac disorders Tachycardia	0.00% 0/15 • Enrollment through study completion (on average 2 months).	0.00% 0/15 • Enrollment through study completion (on average 2 months).	6.7% 1/15 • Number of events 1 • Enrollment through study completion (on average 2 months).
Cardiac disorders dizzyness	6.7% 1/15 • Number of events 1 • Enrollment through study completion (on average 2 months).	0.00% 0/15 • Enrollment through study completion (on average 2 months).	0.00% 0/15 • Enrollment through study completion (on average 2 months).

Additional Information

Belinda Lennerz

Boston Children's Hospital

Phone: 617 355 7476

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place