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

Not Applicable

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Other: high GI meal; Other: low GI meal; Drug: euglycemic insulin clamp; Drug: primed-variable insulin infusion

• Registration Number: NCT02772783
• Lead Sponsor: Boston Children's Hospital

Brief Summary

Processed carbohydrates cause rapid changes in blood sugar and have been associated with overeating and obesity. We have shown that test meals high in processed carbohydrate affect brain areas involved in addiction, craving and overeating. It is unknown whether the changes in blood sugar or the associated higher insulin levels mediate this brain activation and its likely adverse effects.

Answering this question is important for patients with type 1 diabetes who have elevated risks of obesity and disordered eating: If blood sugar is the causal mechanism, optimal insulin coverage should be protective. If insulin is the causal mechanism, however, a diet high in processed carbohydrate could predispose to overeating and weight gain, as this diet requires higher insulin doses.

To disentangle these factors, we will study brain activation and relevant blood markers in 15 men with diabetes. In 4 sessions, we will examine meals with differential carbohydrate properties while giving insulin infusions.

Detailed Description

A total of 15 male participants (age 18-45) with T1DM will be recruited. Participants will be enrolled in the study for a total of 1-3 months, and participate in a pre-test visit and three test visits, each after a 10-12-hr overnight fast. Participants will be instructed to consume their regular, weight maintaining diet between visits.

At the pre-test visit, the study director or PI will meet participants, confirm eligibility and obtain informed consent. Participants will receive a low glycemic index (GI) meal with optimal iv insulin coverage using a negative feedback algorithm to maintain euglycemia (euglycemic clamp). Insulin requirement will be quantified. At some time during the visit, participants will present to the BIDMC research imaging facility for a practice MRI session, during which they will undergo a brief imaging sequence to get accustomed to the scanning process and eliminate anxiety as a confounder of imaging data.

At each of 3 test visits, one of the following experimental conditions will be applied in a randomized, blinded cross-over design: (a) high GI meal with euglycemic clamp, (b) low GI meal with euglycemic clamp, (c) high GI meal with primed-variable insulin infusion at the rate established during the pre-test visit. After steady state is established, baseline laboratory evaluation and MRI imaging will be obtained, followed by the test meal. Imaging will be repeated at 1 and 4 hours postprandial. Blood samples for pertinent metabolic and hormonal parameters will be obtained every 30 minutes. Each test-visit concludes with a standard weighed meal to quantify ad-libitum intake.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-05-11
• Study First Submitted QC: 2016-05-11
• Study First Posted: 2016-05-16
• Study Start: 2016-07
• Primary Completion: 2018-05
• Study Completion: 2018-05
• Results First Submitted: 2020-02-17
• Status Verified: 2021-05
• Results First Submitted QC: 2021-05-25
• Last Update Submitted: 2021-05-25
• Results First Posted: 2021-06-18
• Last Update Posted: 2021-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

Inclusion Criteria

• Type 1 diabetes for a minimum of 3 years
• BMI 20-35 kg/m2
• Use of insulin pump
• Willing and able to: Maintain weight and document for duration of the study

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Exclusion Criteria

• Insulin resistance (current insulin requirement > 1.5 U/kg/d)
• Insulin requirement < 0.5 unit/kg/day (cut-off for preserved beta-cell function)
• HbA1C ≥ 8.0%
• DKA within 2 months
• Frequent hypoglycemia (BG <50 mg/dl), > 3 times per week
• Fluctuations in body weight >10% over preceding year
• Smoking or illicit substance abuse
• High levels of physical activity (≥60 minutes per day, ≥ 4 days per week)
• Current weight loss diet
• Medical problems, medications or dietary supplements that may affect metabolism, insulin action, body weight, appetite, energy expenditure, or gastrointestinal absorption (e.g. celiac disease)
• Allergies to compounds or intolerance of the liquid meals
• MRI exclusion criteria
• Other conditions according to self-report that would prohibit participation based and researcher assessment

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
high GI meal, euglycemic insulin clamp	high GI meal	A nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia.This condition results in euglycemia with high insulin levels.
high GI meal, euglycemic insulin clamp	euglycemic insulin clamp	A nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia.This condition results in euglycemia with high insulin levels.
high GI meal, fixed insulin infusion	high GI meal	A nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously at a rate previously established to maintain euglycemia after a low glycemic index meal. This condition results in moderate hyperglycemia with low insulin levels.
high GI meal, fixed insulin infusion	primed-variable insulin infusion	A nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously at a rate previously established to maintain euglycemia after a low glycemic index meal. This condition results in moderate hyperglycemia with low insulin levels.
low GI meal, euglycemic insulin clamp	low GI meal	A nutritional shake with low GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia. This condition results in euglycemia with low insulin levels.
low GI meal, euglycemic insulin clamp	euglycemic insulin clamp	A nutritional shake with low GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia. This condition results in euglycemia with low insulin levels.

Primary Outcome Measures

Name	Time	Method
Nucleus Accumbens Blood Flow	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.

Secondary Outcome Measures

Name	Time	Method
Blood Flow in Other Brain Areas Involved in Intake Regulation - Dorsal Caudate	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.
Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation	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.
Nucleus Accumbens Blood Flow	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.
Blood Flow in Other Brain Areas Involved in Intake Regulation - Ventrolateral Striatum	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.

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States