Effects of Ketosis on Brain Function in Patients With T1DM

ConditionType1diabetes
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-40
SponsorBoston Children's Hospital

About this trial

The scientific goal of this study is to examine the effects of a ketogenic diet on hypoglycemia tolerance and brain function in people with type 1 diabetes mellitus (T1D) and to clarify the mechanistic role of ketones in this process. Glycemic management of T1D is typified by alternating periods of hyper- and hypo-glycemia. Because brain metabolism under usual conditions depends on glucose, acute hypoglycemia leads to immediate complications including impaired cognitive function and a counter-regulatory hormone response. Recurrent hypoglycemia is associated with functional and structural changes in the brain and contributes to the cognitive decline observed in individuals with diabetes. The state of nutritional ketosis (as it occurs during fasting or when following a ketogenic \[very low carbohydrate\] diet) may protect against these acute and chronic complications. As the body relies on fat metabolism, ketone bodies build up and provide an alternative fuel for the brain. Studies during hypoglycemia have shown better cognitive function and less hypoglycemia symptoms in the setting of nutritional ketosis or with ketone administration. This physiological benefit may have special relevance for people with T1D who experience hypoglycemia frequently. To date, no mechanistic studies have examined brain effects of nutritional ketosis in T1D; nor have any trials explored the potential relevance of this for diabetes care.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Males and females with T1D for at least 1 year

Age 18 to 40 years

Tanner stage ≥ IV

BMI 18.5-35 kg/m2

Disqualifiers

Ketoacidosis or severe hypoglycemia with seizure or coma in the past 6 months

Dietary restrictions or intolerances that are incompatible with the planned food deliveries, e.g. celiac disease, gastroparesis, certain food allergies

Following a weight-loss or otherwise restrictive diet

Vigorous exercise >2 hours on >3 days a week

Trial design

Design model

Parallel

Treatments tested in this trial

  • Very low carbohydrate diet

    Other intervention

    All meals will be delivered and participants will consume study foods exclusively. Participants will receive a fiber supplement with each meal as needed to promote digestive health, and a daily multi-vitamin, magnesium and omega-3 supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 5% carbohydrate, 75% fat, 20% protein.

  • Standard carbohydrate diet

    Other intervention

    All meals will be delivered and participants will consume study foods exclusively. Participants will receive a daily multi-vitamin and omega-3 supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 50% carbohydrate, 30% fat, 20% protein.

Treatment groups

24 Participants
are divided into 2 treatment groups
Group A: Very low carbohydrate dietExperimental treatment 1 intervention
Group B: Standard dietActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Glycemic threshold for hypothalamic activation

The blood glucose level at which hypothalamic activation is detected by continuous BOLD functional MRI during a 40 min glycemic descent from 90 to 50 mg/dL

Time frame
Diet week 5-12

Secondary outcomes

1

Resting brain activation changes in brain areas related to cognition during hypoglycemia

Resting brain activation will be measured by arterial spin labeling (ASL) during euglycemia and hypoglycemia and differences will be reported

Time frame
Diet week 5-12
2

Task-related brain activation changes during hypoglycemia in brain areas related to cognition

Task-related brain activation will be measured during a working memory task (n-back) by BOLD during euglycemia and hypoglycemia and differences will be reported

Time frame
Diet week 5-12
3

Functional connectivity changes in brain areas related to cognition during hypoglycemia

Functional connectivity activation will be measured using resting state functional MRI during euglycemia and hypoglycemia and differences will be reported

Time frame
Diet week 5-12
4

Response time changes during hypoglycemia

Response time to a working-memory cognitive task (n-back) will be measured during hypoglycemia and compared to the response time in euglycemia

Time frame
Diet week 5-12

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Boston Children's Hospital

Lead sponsor

Beth Israel Deaconess Medical Center

Collaborator