Diabetes Mellitus, Type 1
Conditions
Keywords
Type 1 diabetes, Ketogenic diet, Insulin sensitivity, Continuous glucose monitoring, Hypoglycemia
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) 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.
Interventions
BEHAVIORALKetogenic Diet
Participants will consume a very-low-carbohydrate ketogenic diet for 12 weeks.
BEHAVIORALStandard Diet
Participants will consume an American Diabetes Association-recommended standard diet for 12 weeks.
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 whole-body palmitate turnover | Before and immediately after the dietary intervention | Palmitate turnover will be measured by isotope dilution |
| 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 de novo cholesterol synthesis | Before and immediately after the dietary intervention | Cholesterol synthesis will be assessed by the deuterated water method |
| 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 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 intrahepatic triglyceride content | Before and immediately after the dietary intervention | Intrahepatic triglyceride content will be assessed by magnetic resonance imaging (MRI) |
| 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 hs-CRP | Before and immediately after the dietary intervention | Plasma hs-CRP will be measured |
| Change in plasma PAI-1 | Before and immediately after the dietary intervention | Plasma PAI-1 will be measured |
| Change in plasma IL-6 | Before and immediately after the dietary intervention | Plasma IL-6 will be measured |
| Change in plasma TNF-alpha | Before and immediately after the dietary intervention | Plasma TNF-alpha will be measured |
| Change in plasma markers of liver function | Before and immediately after the dietary intervention | Plasma markers of liver function will be measured |
| Change in plasma markers of kidney function | Before and immediately after the dietary intervention | Plasma markers of kidney function 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 percent time in hypoglycemia | Before and immediately after the dietary intervention | Percent time in hypoglycemia will be assessed by using a continuous glucose monitor |
| 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 |
| Level 3 hypoglycemia event rate | During the 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 |
| Diabetic ketoacidosis event rate | During the 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 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 |
| 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 glycated hemoglobin and albumin | Before, during, and immediately after the dietary intervention | Glycated hemoglobin and albumin will be assessed |
Countries
United States
Contacts
CONTACTTara Wilmot, RDN
CONTACTMax C Petersen, MD PhD
PRINCIPAL_INVESTIGATORSamuel Klein, MD
Washington University School of Medicine
Outcome results
None listed