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.

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