The Effects of a Low Carbohydrate, Non-Ketogenic Diet Versus Standard Diabetes Diet on Glycemic Control in Type 1 Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effects of a Low Carbohydrate, Non-Ketogenic Diet Versus Standard Diabetes Diet on Glycemic Control in Type 1 Diabetes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Other: Low carbohydrate diet
* Other: Standard of care diet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Low carbohydrate diet<br> | Other: Low carbohydrate diet<br>* 60-80 g total carbohydrate per day<br>|
| Active Comparator: Experimental: Standard of care diet<br> | Other: Standard of care diet<br>* > 150 g total carbohydrate per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Range | Difference in time spent with glucose values between 70-180 mg/dL assessed by continuous glucose monitoring (CGM) | 5 days of worn CGM during each intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Glucose | Difference in mean glucose values assessed by CGM | Baseline to 12 weeks (1 week worn CGM data) | 
| Standard deviation of glucose | Difference in standard deviation of glucose values assessed by CGM | Baseline to 12 weeks (1 week worn CGM data) | 
| Mean amplitude of glycemic excursions | Difference in mean amplitude of glycemic excursions assessed by CGM | Baseline to 12 weeks (1 week worn CGM data) | 
| Time in hypoglycemia | Difference in time spent with glucose values <70 mg/dL; between 55-70 mg/dL; and <55 mg/dL | Baseline to 12 weeks (1 week worn CGM data) | 
| Time in hyperglycemia | Difference in time spent with glucose values >180 mg/dL | Baseline to 12 weeks (1 week worn CGM data) | 
| Change in HbA1c | Difference in change in hemoglobin A1c | Baseline to 12 weeks | 
| Coefficient of Variation | Estimate of glucose variability calculated by dividing the standard deviation by average glucose | Baseline to 12 weeks (1 week worn CGM data) | 
| Severe hypoglycemia | Difference in number of severe hypoglycemia episodes (glucagon or IV dextrose administration) | Baseline to 12 weeks | 
| Total daily insulin dose | Difference in total daily insulin dose | Baseline to 12 weeks | 
| Total daily basal insulin 24 hour | Difference in total daily basal insulin in 24 hours | Baseline to 12 weeks | 
| Total daily bolus insulin 24 hour | Difference in total daily bolus insulin in 24 hours | Baseline to 12 weeks | 
| Body weight | Change in body weight | Baseline to 12 weeks | 
| Body Mass Index (BMI) | Change in BMI | Baseline to 12 weeks | 
| Systolic Blood Pressure (mm Hg) | Change in systolic BP | Baseline to 12 weeks | 
| Diastolic Blood Pressure (mm Hg) | Change in diastolic BP | Baseline to 12 weeks | 
| Pulse, per minute | Change in pulse | Baseline to 12 weeks | 
| Energy Intake (kcal/day) | Change in energy intake | Baseline to 12 weeks | 
| Daily carbohydrate intake (total carbohydrate, g/day) | Change in carbohydrate intake | Baseline to 12 weeks | 
| Percent energy intake as Carbohydrate | Change in % carbohydrate intake | Baseline to 12 weeks | 
| Daily protein intake (total protein, g/day) and Daily fat intake (total fat, g/day) | Change in protein intake | Baseline to 12 weeks | 
| Fat quality intake (% total fat as monounsaturated, polyunsaturated, saturated, omega-3) | Change in fat quality | Baseline to 12 weeks | 
| Standard Lipid Panel | Change in (Total cholesterol, HDL cholesterol, LDL cholesterol-calculated, triglycerides; mg/dL) | Baseline to 12 weeks | 
| LDL-P (nmol/L) | Change in LDL-P | Baseline to 12 weeks | 
| HDL-P (umol/L) | Change in HDL-P | Baseline to 12 weeks | 
| VLDL-P | Change in VLDL-P (nmol/L) | Baseline to 12 weeks | 
| LDL size | Change in LDL size (nm) | Baseline to 12 weeks | 
| HDL size | Change in HDL size (nm) | Baseline to 12 weeks | 
| VLDL size | Change in VLDL size (nm) | Baseline to 12 weeks | 
| High-sensitive C-reactive protein (hs-CRP) | Change in hs-CRP | Baseline to 12 weeks | 
| Plasma lipopolysaccharide | Surrogate marker for inflammation | Baseline to 12 weeks | 
| Serum Ketones (beta-hydroxybutyrate) | beta-hydroxybutyrate (mmol/L) | Baseline to 12 weeks | 
| Type 1 Diabetes Nutrition Knowledge Survey | Validated nutrition knowledge survey (nutrition label reading, carbohydrate counting) | Baseline to Week 33 (end of study) | 
| Diet Quality | Minerals, Vitamins, Dietary Fiber amounts compared to DRIs for age, ascertained by 3 day 24 hour food logs | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low carbohydrate diet