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

NCT02772783 | Completed Results

• 2 other identifiers: IRB-P00022176IRB- 2016P000079
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

brain; fMRI; carbohydrate; insulin clamp; intake regulation; overweight; glycemic index

Outcome Measures

Primary Outcomes (1)

• Nucleus Accumbens Blood Flow

  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.

  4 hrs postprandial

Secondary Outcomes (5)

• Nucleus Accumbens Blood Flow

  1 hr postprandial

• Blood Flow in Other Brain Areas Involved in Intake Regulation - Dorsal Caudate

  4 hrs postprandial

• Blood Flow in Other Brain Areas Involved in Intake Regulation - Ventrolateral Striatum

  1 hr postprandial

• Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation

  4 hrs postprandial

• Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation

  1 hr postprandial

Other Outcomes (10)

• Plasma Glucose Level

  0-4.5 hrs postprandial

• Serum Insulin Level

  0-4.5 hrs postprandial

• Serum Fatty Acids

  0-4.5 hrs postprandial

Study Arms (3)

high GI meal, euglycemic insulin clamp

EXPERIMENTAL

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.

Other: high GI meal; Drug: euglycemic insulin clamp

high GI meal, fixed insulin infusion

EXPERIMENTAL

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.

Other: high GI meal; Drug: primed-variable insulin infusion

low GI meal, euglycemic insulin clamp

ACTIVE COMPARATOR

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.

Other: low GI meal; Drug: euglycemic insulin clamp

Interventions

high GI meal OTHER

High and low GI liquid test meals are matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals will provide 25% of individual daily energy requirements as estimated by the Harris Benedict equation. A high glycemic index of \~90 is achieved by using corn syrup as a carbohydrate source.

high GI meal, euglycemic insulin clamp; high GI meal, fixed insulin infusion

low GI meal OTHER

High and low GI liquid test meals are matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals will provide 25% of individual daily energy requirements as estimated by the Harris Benedict equation. A low glycemic index of \~40 is achieved by using uncooked corn starch as a carbohydrate source.

low GI meal, euglycemic insulin clamp

euglycemic insulin clamp DRUG

Insulin will be given intravenously for 5 hours. During the entire clamp protocol, glucose levels will be measured every 5 minutes. A basal insulin infusion will be started at 80% of the patients insulin pump basal rate, and will be adjusted between 0.1 and 2.5 mU/kg•min, depending upon the patient's plasma glucose level in relation to the target range target of 90-100 mg/dl.

high GI meal, euglycemic insulin clamp; low GI meal, euglycemic insulin clamp

primed-variable insulin infusion DRUG

A primed-variable infusion of insulin will be administered at the rate established to achieve euglycemia after a low glycemic index meal. This is expected to result in moderate hyperglycemia as the high GI meal is associated with higher insulin requirements. For patient safety, glucose levels will be measured every 30 minutes. If glucose levels are \> 400 mg/dl or \< 60 mg/dl, insulin infusion will be adjusted to maintain glucose levels target of 60-400 mg/dl.

high GI meal, fixed insulin infusion

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• Other conditions according to self-report that would prohibit participation based and researcher assessment

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator
• Brigham and Women's Hospital: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Overweight

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Belinda Lennerz
• Organization: Boston Children's Hospital

belinda.lennerz@childrens.harvard.edu

617 355 7476

Study Officials

• Belinda S Lennerz, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor in Pediatric Endocrinology

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: May 16, 2016
• Study Start: July 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: June 18, 2021
• Results First Posted: June 18, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)