Clinical trial NCT02772783: Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus
Official title: Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Keywords: brain
fMRI
carbohydrate
insulin clamp
intake regulation
overweight
glycemic index
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Brigham and Women's Hospital
First posted: 2016-05-16
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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
* MRI exclusion criteria
* Other conditions according to self-report that would prohibit participation based and researcher assessment

Primary outcomes:
measure: Nucleus Accumbens Blood Flow
timeFrame: 4 hrs postprandial
Secondary outcomes:
measure: Nucleus Accumbens Blood Flow
timeFrame: 1 hr postprandial
measure: Blood Flow in Other Brain Areas Involved in Intake Regulation - Dorsal Caudate
timeFrame: 4 hrs postprandial
measure: Blood Flow in Other Brain Areas Involved in Intake Regulation - Ventrolateral Striatum
timeFrame: 1 hr postprandial
measure: Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation
timeFrame: 4 hrs postprandial
measure: Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation
timeFrame: 1 hr postprandial
Other outcomes:
measure: Plasma Glucose Level
timeFrame: 0-4.5 hrs postprandial
measure: Serum Insulin Level
timeFrame: 0-4.5 hrs postprandial
measure: Serum Fatty Acids
timeFrame: 0-4.5 hrs postprandial
measure: Plasma Ghrelin
timeFrame: 0-4.5 hrs postprandial
measure: Plasma GLP-1
timeFrame: 0-4.5 hrs postprandial
measure: Plasma PYY
timeFrame: 0-4.5 hrs postprandial
measure: Plasma CCK
timeFrame: 0-4.5 hrs postprandial
measure: Plasma Glucagon
timeFrame: 0-4.5 hrs postprandial
measure: Plasma Leptin
timeFrame: 0-4.5 hrs postprandial
measure: Metabolomics
timeFrame: 0, 1 and 4 hrs postprandial
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Belinda S Lennerz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: