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

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ClinicalTrials.gov Identifier: NCT02772783
Recruitment Status : Completed
First Posted : May 16, 2016
Last Update Posted : May 8, 2018
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Information provided by (Responsible Party):
Belinda Lennerz, 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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Other: high GI meal Other: low GI meal Drug: euglycemic insulin clamp Drug: primed-variable insulin infusion Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus
Study Start Date : July 2016
Actual Primary Completion Date : May 2018
Actual Study Completion Date : May 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: 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.
Other: 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.

Drug: 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.

Experimental: 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.
Other: 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.

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.

Active Comparator: 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.
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.

Drug: 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.




Primary Outcome Measures :
  1. Nucleus Accumbens blood flow (right and left) [ Time Frame: 4 hrs postprandial ]
    by arterial spin labeling (MRI)


Secondary Outcome Measures :
  1. Nucleus Accumbens blood flow [ Time Frame: 1 hr postprandial ]
    by arterial spin labeling (ASL) MRI

  2. blood flow in other brain areas involved in intake regulation [ Time Frame: 4 hrs postprandial ]
    by ASL

  3. blood flow in other brain areas involved in intake regulation [ Time Frame: 1 hr postprandial ]
    by ASL

  4. functional connectivity of Nucleus Accumbens, Hypothalamus and other brain areas involved in intake regulation [ Time Frame: 4 hrs postprandial ]
    by resting state functional MRI (rs-fMRI)

  5. functional connectivity of Nucleus Accumbens, Hypothalamus and other brain areas involved in intake regulation [ Time Frame: 1 hr postprandial ]
    by rs-fMRI


Other Outcome Measures:
  1. plasma glucose level [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes

  2. serum insulin level [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes

  3. serum fatty acids [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes

  4. plasma ghrelin [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel

  5. plasma GLP-1 [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel

  6. plasma PYY [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel

  7. plasma CCK [ Time Frame: 0-4.5 hrs postprandial ]
    analyzed as part of a metabolic hormone panel

  8. plasma glucagon [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel

  9. plasma leptin [ Time Frame: 0-4.5 hrs postprandial ]
    analyzed as part of a metabolic hormone panel

  10. metabolomics [ Time Frame: 0, 1 and 4 hrs postprandial ]
    LC-MS/MS methodology using several chromatographic stationary phases for > 400 metabolites



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  • MRI exclusion criteria
  • Other conditions according to self-report that would prohibit participation based and researcher assessment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02772783


Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children’s Hospital
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Investigators
Principal Investigator: Belinda S Lennerz, MD, PhD Boston Children’s Hospital

Responsible Party: Belinda Lennerz, Instructor in Pediatric Endocrinology, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT02772783     History of Changes
Other Study ID Numbers: IRB-P00022176
IRB- 2016P000079 ( Other Identifier: Beth Israel Deaconess Medical Center )
First Posted: May 16, 2016    Key Record Dates
Last Update Posted: May 8, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Belinda Lennerz, Boston Children’s Hospital:
brain
fMRI
carbohydrate
insulin clamp
intake regulation
overweight
glycemic index

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs