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

Boston Children's Hospital

Status: Completed

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: euglycemic insulin clamp; Other: low GI meal; Drug: primed-variable insulin infusion; Other: high GI meal

Study type: Interventional

Funder types: Other

Identifiers

NCT02772783

IRB- 2016P000079 (Other Identifier)

IRB-P00022176

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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15 participants in 3 patient groups

high GI meal, euglycemic insulin clamp

Experimental group

Description:

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.

Treatment:

Drug: euglycemic insulin clamp

Other: high GI meal

high GI meal, fixed insulin infusion

Experimental group

Description:

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.

Treatment:

Drug: primed-variable insulin infusion

Other: high GI meal

low GI meal, euglycemic insulin clamp

Active Comparator group

Description:

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.

Treatment:

Drug: euglycemic insulin clamp

Other: low GI meal