Efficacy and Safety of a Ketogenic Diet in Type 1 Diabetes

Washington University School of Medicine58 enrolled

Overview

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.

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) have evaluated the efficacy of KD for \>7 days in people with T1D. In addition, there are serious concerns regarding the safety and tolerability of a KD in patients with T1D, including the potential for an increased risk of hypoglycemia, diabetic ketoacidosis, dyslipidemia, insulin resistance, decreased bone mineral density, and impaired quality of life. This study is a 12-week RCT to evaluate the clinical efficacy, metabolic function, safety, socio-behavioral impact, acceptability and potential for dissemination of an isocaloric KD compared with an American Diabetes Association-recommended control diet in adults with T1D.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 1

Interventions

Ketogenic DietBEHAVIORAL

Participants will consume a very-low-carbohydrate ketogenic diet for 12 weeks.

Standard DietBEHAVIORAL

Participants will consume an American Diabetes Association-recommended standard diet for 12 weeks.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

RECRUITING

Outcomes

Primary Outcomes

Change in continuous glucose monitor (CGM) time-in-range

Interstitial glucose percent time in range assessed by using a continuous glucose monitor

Time frame: Before and immediately after the dietary intervention

Change in skeletal muscle insulin sensitivity

Insulin sensitivity will be determined by the hyperinsulinemic-euglycemic clamp procedure

Time frame: Before and immediately after the dietary intervention

Secondary Outcomes

Change in daily insulin requirements

The daily total dose of insulin used will be assessed

Time frame: Assessed before, during, and immediately after the dietary intervention

Change in 24-hour glucose concentrations

Plasma glucose concentrations will be evaluated from frequent blood samples over a 24 hour period

Time frame: Before and immediately after the dietary intervention

Change in 24-hour glucagon concentrations

Plasma glucagon concentrations will be evaluated from frequent blood samples over a 24 hour period

Time frame: Before and immediately after the dietary intervention

Change in whole-body palmitate turnover

Palmitate turnover will be measured by isotope dilution

Time frame: Before and immediately after the dietary intervention

Change in plasma lipid profile

Fasting plasma lipid profile will be assessed

Time frame: Before and immediately after the dietary intervention

Central Contacts

Tara Wilmot, RDN

CONTACT

314-399-8576 tara.wilmot@wustl.edu

Max C Petersen, MD PhD

CONTACT

314-362-8450 max.p@wustl.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Change in hepatic de novo lipogenesis

Hepatic de novo lipogenesis will be assessed by the deuterated water method

Time frame: Before and immediately after the dietary intervention

Change in de novo cholesterol synthesis

Cholesterol synthesis will be assessed by the deuterated water method

Time frame: Before and immediately after the dietary intervention

Change in fat mass

Fat mass will be assessed using dual-energy x-ray absorptiometry (DXA)

Time frame: Before and immediately after the dietary intervention

Change in fat-free mass

Fat-free mass will be assessed using dual-energy x-ray absorptiometry (DXA)

Time frame: Before and immediately after the dietary intervention

Change in intrahepatic triglyceride content

Intrahepatic triglyceride content will be assessed by magnetic resonance imaging (MRI)

Time frame: Before and immediately after the dietary intervention

Change in specific adipose tissue volumes

Specific adipose tissue depot volumes will be assessed by magnetic resonance imaging (MRI)

Time frame: Before and immediately after the dietary intervention

Change in plasma hs-CRP

Plasma hs-CRP will be measured

Time frame: Before and immediately after the dietary intervention

Change in plasma PAI-1

Plasma PAI-1 will be measured

Time frame: Before and immediately after the dietary intervention

Change in plasma IL-6

Plasma IL-6 will be measured

Time frame: Before and immediately after the dietary intervention

Change in plasma TNF-alpha

Plasma TNF-alpha will be measured

Time frame: Before and immediately after the dietary intervention

Change in plasma markers of liver function

Plasma markers of liver function will be measured

Time frame: Before and immediately after the dietary intervention

Change in plasma markers of kidney function

Plasma markers of kidney function will be measured

Time frame: Before and immediately after the dietary intervention

Change in plasma markers of bone turnover

Plasma markers of bone turnover will be measured

Time frame: Before and immediately after the dietary intervention

Change in percent time in hypoglycemia

Percent time in hypoglycemia will be assessed by using a continuous glucose monitor

Time frame: Before and immediately after the dietary intervention

Change in percent time in hyperglycemia

Percent time in hyperglycemia will be assessed by using a continuous glucose monitor

Time frame: Before and immediately after the dietary intervention

Level 3 hypoglycemia event rate

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

Time frame: During the dietary intervention

Diabetic ketoacidosis event rate

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

Time frame: During the dietary intervention

Change in bone mineral density

Bone mineral density will be assessed using dual-energy x-ray absorptiometry (DXA)

Time frame: Before and immediately after the dietary intervention

Change in sociobehavioral factors

Sociobehavioral factors will be assessed by using validated questionnaires

Time frame: Before and immediately after the dietary intervention

Knowledge and perceptions of the diet

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

Time frame: Immediately after the dietary intervention

Adaptations needed to implement the diet at the population level

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

Time frame: Immediately after the dietary intervention

Change in glycated hemoglobin and albumin

Glycated hemoglobin and albumin will be assessed

Time frame: Before, during, and immediately after the dietary intervention