RECRUITINGINTERVENTIONAL

Effects of Ketosis on Brain Function in Patients With T1DM

Brain Function, Cognition, and Hypoglycemia Tolerance in Patients With Type 1 Diabetes Mellitus in the Setting of Nutritional Ketosis Versus Standard Carbohydrate Diet

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.

Who May Be Eligible (Plain English)

Who May Qualify: - Males and females with T1D for at least 1 year - Age 18 to 40 years - Tanner stage ≥ IV - BMI 18.5-35 kg/m2 - Stable glycemic control (HbA1c 6.5-9%) - Use of a continuous glucose monitor (CGM) - Use of an insulin pump - Attendance of at least 1 diabetes care visit over the past 12 months (including virtual) Who Should NOT Join This Trial: - 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 - History of an eating disorder or at risk for eating disorder, assessed by the Eating Disorders Diagnostic Scale (EDDS) - Major medical illness or use of medications other than insulin and metformin that could interfere with metabolic or glycemic variables - Significant psychiatric illness - Smoking, use of recreational drugs, or excessive alcohol consumption - Pregnancy or breastfeeding - Anemia - For participants who undergo MRI: 1. Standard MRI exclusion criteria 2. Irregular menses 3. Use of psychotropic medication other than SSRIs or other mild antidepressant or anxiety medications (unless these medications are safe to be held for several days to allow for the acquisition of MRI data). Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Males and females with T1D for at least 1 year * Age 18 to 40 years * Tanner stage ≥ IV * BMI 18.5-35 kg/m2 * Stable glycemic control (HbA1c 6.5-9%) * Use of a continuous glucose monitor (CGM) * Use of an insulin pump * Attendance of at least 1 diabetes care visit over the past 12 months (including virtual) Exclusion Criteria: * 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 * History of an eating disorder or at risk for eating disorder, assessed by the Eating Disorders Diagnostic Scale (EDDS) * Major medical illness or use of medications other than insulin and metformin that could interfere with metabolic or glycemic variables * Significant psychiatric illness * Smoking, use of recreational drugs, or excessive alcohol consumption * Pregnancy or breastfeeding * Anemia * For participants who undergo MRI: 1. Standard MRI exclusion criteria 2. Irregular menses 3. Use of psychotropic medication other than SSRIs or other mild antidepressant or anxiety medications (unless these medications are safe to be held for several days to allow for the acquisition of MRI data).

Treatments Being Tested

OTHER

Very low carbohydrate diet

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.

OTHER

Standard carbohydrate diet

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.

Locations (1)

Boston Childrens Hospital

Boston, Massachusetts, United States