The Effects of a Low Carbohydrate, Non-Ketogenic Diet Versus Standard Diabetes Diet on Glycemic Control in Type 1 Diabetes (T1DLoCHO)

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Other: Low carbohydrate diet; Other: Standard of care diet

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • University of Oklahoma Harold Hamm Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Investigators: Principal Investigator: Christina M Crowder, RDN, CNSC, LD, University of Oklahoma

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): June 28, 2019
• Study Completion (Actual): June 28, 2019

Study Registration Dates

• First Submitted: May 7, 2018
• First Submitted That Met QC Criteria: May 31, 2018
• First Posted (Actual): June 4, 2018

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Low carbohydrate diet
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 8840

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No