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OpenTrials
Completed

NCT Number: NCT02772783

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

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.

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Key information

Conditions

Diabetes Mellitus, Type 1 Autoimmune Diseases Body Weight Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

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.

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.

Primary outcomes

  1. Nucleus Accumbens Blood Flow

    Time frame: 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 outcomes

  1. Nucleus Accumbens Blood Flow

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

Other outcomes

  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

Sponsors and collaborators

Lead sponsor

Boston Children's Hospital

Other

Collaborators

  • Beth Israel Deaconess Medical Center
  • Brigham and Women's Hospital

Registry information

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
May 16, 2016
Registry last updated
Jun 18, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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