Efficacy and Safety of a Ketogenic Diet in Type 1 Diabetes
- Conditions
- Interventions
- Registration Number
- NCT06503809
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
Despite strong evidence that tight control of blood sugar reduces the risk of diabetes complications, most people with type 1 diabetes do not achieve recommended blood sugar targets. This randomized controlled trial will test whether a very-low- carbohydrate ketogenic diet can effectively and safely improve blood sugar control in adults with type 1 diabetes.
- Detailed Description
A very-low-carbohydrate ketogenic diet (≤50 g carbohydrate/day) could reduce glycemic variability, total daily insulin requirement, and HbA1c in people with type 1 diabetes (T1D). Indeed, several case series and observational studies of using a ketogenic diet (KD) in people with T1D have observed such benefits. However, no randomized controlled trials (RCTs)...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 58
- Age ≥18 and ≤65 years
- T1D diagnosed >1 year prior to screening
- HbA1c 7.0%-9.0%
- Stable insulin delivery method for the past 30 days
- Ability to read all device instructions and insulin pump settings
- eGFR ≥60 mL/min/1.73 m2
- Use of an insulin pump or insulin delivery by multiple daily injections
- Use of personal CGM for at least 12 weeks and willing to change to Dexcom CGM for the duration of the study, if using a different sensor, to reduce variability in glucose values associated with different CGM products
- Use of cellular phone with data capability for wireless connectivity to the CGM system.
- Body mass index <20.0 or >34.9 kg/m2
- Severe gastroparesis or history of bariatric surgery
- Diabetes-related hospitalization (including for diabetic ketoacidosis or severe hypoglycemia) within 12 months of screening
- Poorly controlled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg)
- Taking diabetes medications, other than insulin (particularly SGLT2 inhibitors, which are associated with an increased risk of euglycemic DKA)
- Structured exercise >210 minutes per week
- Pregnant, lactating, not using effective birth control if premenopausal, or planning to become pregnant within the 6-month study period
- Unstable weight (>4% change in the last 2 months)
- Significant organ system dysfunction (e.g., severe pulmonary, renal, hepatic, or cardiovascular disease)
- Anemia (Hgb <10 g/dL)
- Major psychiatric illness
- Active tobacco use (>8 cigarettes/day) or illegal drug use
- Regular alcohol consumption (>10 standard drinks per week)
- Use of medications known to affect the study outcome measures or increase the risk of study procedures that cannot be temporarily discontinued for this study
- Familial hypercholesterolemia
- Active eating disorder
- Dietary restrictions incompatible with a very-low-carbohydrate KD, vegan diet, vegetarian diet, severe lactose intolerance, severe aversion/sensitivity to eggs, fish, nuts, wheat, or soy, and any anaphylactic food allergy
- Already consuming a low-carbohydrate (<130 g/day) diet
- Persons who are not able to grant voluntary informed consent
- Persons who are unable or unwilling to follow the study protocol or who, for any reason, the research team considers an inappropriate candidate for the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard Care Standard Diet The Standard Care group will consume a diet consistent with the guidelines recommended by the American Diabetes Association that is high in non-starchy vegetables and lean protein sources and low in added sugar. Participants will receive isocaloric packed-out meals for 26 weeks. Ketogenic Diet Ketogenic Diet The Ketogenic Diet group will consume a very-low carbohydrate diet (\<50 g/day) diet. Participants will receive isocaloric packed-out meals for 26 weeks.
- Primary Outcome Measures
Name Time Method Change in continuous glucose monitor (CGM) time-in-range Before and immediately after the dietary intervention Interstitial glucose percent time in range assessed by using a continuous glucose monitor
Change in skeletal muscle insulin sensitivity Before and immediately after the dietary intervention Insulin sensitivity will be determined by the hyperinsulinemic-euglycemic clamp procedure
- Secondary Outcome Measures
Name Time Method Change in plasma markers of kidney function Before and immediately after the dietary intervention Plasma markers of kidney function will be measured
Change in de novo cholesterol synthesis Before and immediately after the dietary intervention Cholesterol synthesis will be assessed by the deuterated water method
Change in plasma PAI-1 Before and immediately after the dietary intervention Plasma PAI-1 will be measured
Change in plasma TNF-alpha Before and immediately after the dietary intervention Plasma TNF-alpha will be measured
Change in percent time in hypoglycemia Before and immediately after the dietary intervention Percent time in hypoglycemia will be assessed by using a continuous glucose monitor
Diabetic ketoacidosis event rate During the 26-week dietary intervention Number of diabetic ketoacidosis event rates defined as plasma beta-hydroxybutyrate concentration \>3 mmol/L, plasma bicarbonate concentration \< 18 mmol/L, pH\<7.30, and symptoms including polyuria, polydipsia, nausea, vomiting, or abdominal pain
Change in bone mineral density Before and immediately after the dietary intervention Bone mineral density will be assessed using dual-energy x-ray absorptiometry (DXA)
Change in 24-hour glucagon concentrations Before and immediately after the dietary intervention Plasma glucagon concentrations will be evaluated from frequent blood samples over a 24 hour period
Change in plasma lipid profile Before and immediately after the dietary intervention Fasting plasma lipid profile will be assessed
Change in hepatic de novo lipogenesis Before and immediately after the dietary intervention Hepatic de novo lipogenesis will be assessed by the deuterated water method
Change in intrahepatic triglyceride content Before and immediately after the dietary intervention Intrahepatic triglyceride content will be assessed by magnetic resonance imaging (MRI)
Change in plasma markers of liver function Before and immediately after the dietary intervention Plasma markers of liver function will be measured
Change in 24-hour glucose concentrations Before and immediately after the dietary intervention Plasma glucose concentrations will be evaluated from frequent blood samples over a 24 hour period
Change in fat-free mass Before and immediately after the dietary intervention Fat-free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Change in specific adipose tissue volumes Before and immediately after the dietary intervention Specific adipose tissue depot volumes will be assessed by magnetic resonance imaging (MRI)
Change in plasma IL-6 Before and immediately after the dietary intervention Plasma IL-6 will be measured
Change in plasma markers of bone turnover Before and immediately after the dietary intervention Plasma markers of bone turnover will be measured
Change in daily insulin requirements Assessed before, during, and immediately after the dietary intervention The daily total dose of insulin used will be assessed
Change in whole-body palmitate turnover Before and immediately after the dietary intervention Palmitate turnover will be measured by isotope dilution
Change in fat mass Before and immediately after the dietary intervention Fat mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Change in plasma hs-CRP Before and immediately after the dietary intervention Plasma hs-CRP will be measured
Level 3 hypoglycemia event rate During the 26-week dietary intervention Number of event rates for level 3 hypoglycemia defined as blood glucose or sensor glucose concentration \<54 mg/dL with neurological symptoms of low blood glucose concentration such as confusion, lethargy, seizure, or coma
Adaptations needed to implement the diet at the population level Immediately after the dietary intervention Qualitative interviews will be performed to understand perceptions of the diet interventions and what adaptations might be needed to disseminate the intervention at a population level
Change in percent time in hyperglycemia Before and immediately after the dietary intervention Percent time in hyperglycemia will be assessed by using a continuous glucose monitor
Change in sociobehavioral factors Before and immediately after the dietary intervention Sociobehavioral factors will be assessed by using validated questionnaires
Knowledge and perceptions of the diet Immediately after the dietary intervention Dissemination and implementation (D\&I) survey measures available from the Washington University Center for Diabetes Translation Research D\&I Core will be used to assess participants' knowledge and perceptions of the diets at the end of the study
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States