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

NCT ID: NCT02772783

Last Updated: 2021-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2018-05-31

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.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

high GI meal, 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.

Group Type: EXPERIMENTAL

high GI meal

Intervention Type: 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.

euglycemic insulin clamp

Intervention Type: 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, fixed 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.

Group Type: EXPERIMENTAL

high GI meal

Intervention Type: 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.

primed-variable insulin infusion

Intervention Type: 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.

low GI meal, 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.

Group Type: ACTIVE_COMPARATOR

low GI meal

Intervention Type: 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.

euglycemic insulin clamp

Intervention Type: 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.

Interventions

high GI meal

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.

Intervention Type: OTHER

low GI meal

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.

Intervention Type: OTHER

euglycemic insulin clamp

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.

Intervention Type: DRUG

primed-variable insulin infusion

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.

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Belinda Lennerz

Instructor in Pediatric Endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Belinda S Lennerz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB- 2016P000079

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-P00022176

Identifier Type: -

Identifier Source: org_study_id