Clinical trial NCT03544892: The Effects of a Low Carbohydrate, Non-Ketogenic Diet Versus Standard Diabetes Diet on Glycemic Control in Type 1 Diabetes
Official title: The Effects of a Low Carbohydrate, Non-Ketogenic Diet Versus Standard Diabetes Diet on Glycemic Control in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Keywords: Low carbohydrate diet
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
First posted: 2018-06-04
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study uses 33 week randomized, powered study design to measure glycemic control with a low carbohydrate dietary pattern versus standard of care diabetes medical nutrition therapy. Each arm is 12 weeks with an 8 week washout between arms.
Primary purpose: TREATMENT

Brief summary: This randomized, crossover nutrition intervention seeks to examine the effects of a non-ketogenic low carbohydrate (CHO) diet (60-80g per day) on glycemic control, lipids, and markers on inflammation in individuals with Type 1 Diabetes (T1D). This study will be used to inform clinical practice, especially in teaching medical nutrition therapy to new-onset diabetes patients and those struggling with glycemic control and hyperlipidemia. At this time, no evidenced-based universal recommendations from randomized controlled trials exist to support low carbohydrate dietary patterns as a front-line approach in individuals with T1D. The investigators hypothesize a diet consisting of 60-80 g carbohydrate diet will result in greater improvement in glycemic control compared to a 50% carbohydrate diet in patients with Type 1 diabetes over 12 weeks in the outpatient setting.

Detailed description: Type 1 diabetes mellitus (T1D) is marked by total insulin dependence with challenges regarding glycemic control and concomitant sequela. While standard of care medical nutrition therapy for this disease centers on matching carbohydrate to insulin at meals, recent literature and clinical reports have shown superior glycemic control and cardiovascular measures with lower carbohydrate dietary patterns (\<130g/day) as compared to the standard American MyPlate (50% total calories as carbohydrate) approach. Diabetes management has evolved tremendously in the last twenty years with the development of sophisticated insulin pumps and continuous glucose monitors; but, glycemic control is still dependent on quantification of carbohydrate, imperfect in the real-world setting. Due to inherent error in carbohydrate counting, the investigators propose that less carbohydrate will produce better glycemic control by minimizing error and subsequent variation in individuals with type 1 diabetes.

There has long been a movement in the medical community to prescribe low carbohydrate diets under the premise of "less carbohydrate, less insulin, less glycemic variation". This strategy centers on "the law of small numbers", a calculus principle describing magnitude of variation in the output (glycemic variation) as the function of input size (CHO + insulin). Carbohydrate counting tends to result in \~50% error while there is \~30% variation in insulin action, making exactitude impossible. However, low CHO diets tend to provide \>40% energy from fat due to the macronutrient distribution. With innate risk of cardiovascular disease in T1D, standard of care has supported restriction of total fat consumption, especially saturated fat, in effort to control cholesterol. While the American Diabetes Association recognizes that dietary fat is a controversial and complex issue, eliminating trans-fats is the only consensus point across the field. To date, most low CHO diet studies in both T1D and Type 2 Diabetes (T2D) have not shown adverse effects on lipids and tend to show decreases in triglycerides and either no change or increases in HDL, LDL, and total cholesterol.

Eligibility criteria: Inclusion Criteria:

* Confirmed Type 1 diabetes for \> 1 year confirmed by physician diagnosis
* HbA1c \>5.9% and \<10%;
* Confirmation of minimum three blood glucose tests per day (meter download or chart record)
* Use of continuous subcutaneous insulin infusion therapy (CSII) or multiple daily injection (MDI) intensive insulin therapy
* No change in insulin therapy type (CSII or MDI) in last 2 months or longer
* Willingness to count carbohydrate and use bolus calculator on insulin pump during the intervention periods
* Willingness to wear a 7 day CGM at three different time points during the study

Exclusion Criteria:

* Females of childbearing potential who are pregnant or intend to become pregnant, are exclusively breastfeeding, or who are not using adequate contraceptive methods
* Use of corticosteroids during or within 30 days prior to the intervention periods
* Macroalbuminuria
* Active proliferative retinopathy combined with an HbA1c ≥ 9%
* Known or suspected alcohol or drug abuse
* Other concomitant medical or psychological condition that according to the investigator's assessment makes the patient unsuitable for study participation

Primary outcomes:
measure: Time in Range
timeFrame: 5 days of worn CGM during each intervention
Secondary outcomes:
measure: Mean Glucose
timeFrame: Baseline to 12 weeks (1 week worn CGM data)
measure: Standard deviation of glucose
timeFrame: Baseline to 12 weeks (1 week worn CGM data)
measure: Mean amplitude of glycemic excursions
timeFrame: Baseline to 12 weeks (1 week worn CGM data)
measure: Time in hypoglycemia
timeFrame: Baseline to 12 weeks (1 week worn CGM data)
measure: Time in hyperglycemia
timeFrame: Baseline to 12 weeks (1 week worn CGM data)
measure: Change in HbA1c
timeFrame: Baseline to 12 weeks
measure: Coefficient of Variation
timeFrame: Baseline to 12 weeks (1 week worn CGM data)
measure: Severe hypoglycemia
timeFrame: Baseline to 12 weeks
measure: Total daily insulin dose
timeFrame: Baseline to 12 weeks
measure: Total daily basal insulin 24 hour
timeFrame: Baseline to 12 weeks
measure: Total daily bolus insulin 24 hour
timeFrame: Baseline to 12 weeks
measure: Body weight
timeFrame: Baseline to 12 weeks
measure: Body Mass Index (BMI)
timeFrame: Baseline to 12 weeks
measure: Systolic Blood Pressure (mm Hg)
timeFrame: Baseline to 12 weeks
measure: Diastolic Blood Pressure (mm Hg)
timeFrame: Baseline to 12 weeks
measure: Pulse, per minute
timeFrame: Baseline to 12 weeks
measure: Energy Intake (kcal/day)
timeFrame: Baseline to 12 weeks
measure: Daily carbohydrate intake (total carbohydrate, g/day)
timeFrame: Baseline to 12 weeks
measure: Percent energy intake as Carbohydrate
timeFrame: Baseline to 12 weeks
measure: Daily protein intake (total protein, g/day) and Daily fat intake (total fat, g/day)
timeFrame: Baseline to 12 weeks
measure: Fat quality intake (% total fat as monounsaturated, polyunsaturated, saturated, omega-3)
timeFrame: Baseline to 12 weeks
measure: Standard Lipid Panel
timeFrame: Baseline to 12 weeks
measure: LDL-P (nmol/L)
timeFrame: Baseline to 12 weeks
measure: HDL-P (umol/L)
timeFrame: Baseline to 12 weeks
measure: VLDL-P
timeFrame: Baseline to 12 weeks
measure: LDL size
timeFrame: Baseline to 12 weeks
measure: HDL size
timeFrame: Baseline to 12 weeks
measure: VLDL size
timeFrame: Baseline to 12 weeks
measure: High-sensitive C-reactive protein (hs-CRP)
timeFrame: Baseline to 12 weeks
measure: Plasma lipopolysaccharide
timeFrame: Baseline to 12 weeks
measure: Serum Ketones (beta-hydroxybutyrate)
timeFrame: Baseline to 12 weeks
measure: Type 1 Diabetes Nutrition Knowledge Survey
timeFrame: Baseline to Week 33 (end of study)
measure: Diet Quality
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Tulsa
country: United States
facility: University of Oklahoma Harold Hamm Diabetes Center
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: Christina M Crowder, RDN, CNSC, LD
role: PRINCIPAL_INVESTIGATOR
References: