Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

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.
    

Intervention name(s): high GI meal; low GI meal; euglycemic insulin clamp; primed-variable insulin infusion
Intervention type(s): Other; Other; Drug; Drug
Intervention description(s): 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.; 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.; 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.; 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 MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: brain; fMRI; carbohydrate; insulin clamp; intake regulation; overweight; glycemic index