Comparison of Low, Moderate and High Carbohydrate Diet on Insulin Requirements and Metabolic Control in Type 1 Diabetes

Study Overview
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Brief Summary
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The scientific basis for dietary recommendations in type 1 diabetes is almost lacking, with the current recommendations being based on type 2 diabetes studies. Therefore the overall purpose of this study is to improve the current evidence for dietary recommendations to people with type 1 diabetes. Study aim: To compare how a strictly low carbohydrate diet, a moderately low carbohydrate diet and a traditional diabetes diet (with higher amounts of carbohydrates) affect insulin requirements and metabolic control in individuals with type 1 diabetes. Carbohydrate intake is 50-60% of the total energy intake in the traditional diabetes diet, 30-40% in the moderately low carbohydrate diet and 15-20% in the strictly low carbohydrate diet with a minimum of 50 g carbohydrates/day. A diet with less than 50 g carbohydrates/day is usually called very low carbohydrate diet or ketogenic and will not be tested in this study. Those who wish to participate and meet the inclusion criteria (and none of the exclusion criteria) will be randomized to one of the three diets. The duration of the intervention is 6 months after which the participants will be able to choose their own diet for another 6 months. The main study visits are at baseline (screening and study start), 3, 6, 9, and 12 months. Shorter visits will be at 3 and 6 weeks. The participants will meet with a study nurse, dietitian and doctor. They will attend two carbohydrate counting courses before the start of the intervention in order to be able to match their insulin to the amount carbohydrates they eat. Participants will receive written materials about their diets with menus and recipes for better adherence to the diet. The primary endpoint is the change in insulin requirements within and between groups (for secondary endpoints please see relevant section). For assessing the different endpoints the participants will provide blood, urine and feces samples for lab analyses as well as register their insulin use, blood glucose, diet, physical activity and any blood ketones or hypoglycemia electronically or in written forms. Continuous/flash glucose monitoring (CGM/FGM) will be also used. Dietary assessment and adherence will be based on 3-4 day food diaries before every scheduled study visit.

Official Title
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DANCE (Diabetes ANd CarbohydratEs). Does the Amount of Dietary Carbohydrates Affect Insulin Requirements and Metabolic Control in Type 1 Diabetes? Comparative Study of Traditional Diabetes, Moderately Low and Strictly Low Carbohydrate Diet

Conditions
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Type1diabetes

Intervention / Treatment
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* Behavioral: traditional diabetes diet
* Behavioral: moderately low carbohydrate diet
* Behavioral: strictly low carbohydrate diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To have had type 1 diabetes for at least 1 year Age >=20 years old Exclusion Criteria: Cardiovascular disease NYHA class IIIB or more Kidney disease > stadium 3 Liver disease, alanine aminotransferase (ALAT) ≥ 2 µkat/L, BMI < 18.5 kg/m^2 c-peptide ≥ 0.3 nmol/l Pregnant/breastfeeding women, women that plan to get pregnant during study period Other circumstances, which, according to the examiner, make it difficult for an individual to participate.

Ages Eligible for Study
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Minimum Age: 20 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: traditional diabetes diet<br>Participants in this arm will follow a diet with carbohydrate intake 50-60% of total energy intake | Behavioral: traditional diabetes diet<br>* Diet with carbohydrate content 50-60% of total energy intake<br>|
| Experimental: moderately low carbohydrate diet<br>Participants in this arm will follow a diet with carbohydrate intake 30-40% of total energy intake | Behavioral: moderately low carbohydrate diet<br>* Diet with carbohydrate content 30-40% of total energy intake<br>|
| Experimental: strictly low carbohydrate diet<br>Participants in this arm will follow a diet with carbohydrate intake 15-20% of total energy intake | Behavioral: strictly low carbohydrate diet<br>* Diet with carbohydrate content 15-20% of total energy intake<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin use | measured in international units (IU) and percentage. | screening, day 0, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | mmol/mol | screening, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 
| Change in concentration of total cholesterol | mmol/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Change in concentration of triglycerides | mmol/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Change in concentration of HDL-cholesterol | mmol/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Change in concentration of LDL-cholesterol | mmol/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Ratio of LDL/HDL | absolute number | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of glucagon | pmol/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Change in markers of glycemic variability (TIR, TAR, TBR, mean sensor glucose with SD, CV) | mmol/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Change in weight | kg | screening, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 
| Change in BMI | kg/m^2 | screening, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 
| Change in abdominal circumference | cm | screening, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 
| Change in concentration of p-creatinine | micromol/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Change in estimated Glomerular Filtration Rate (eGFR) | mL/min/1,73 m2 | screening, 3 months, 6 months, 9 months, 12 months | 
| Change in microalbuminuria | morning U-Alb/Crea (mg/mmol) | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of Insulin-like Growth Factor 1 (IGF-I) | microg/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of Insulin-like Growth Factor - binding protein 1 (IGFBP-1) | microg/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of leptin | microg/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of adiponectin | mg/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of interleukin 6 (IL-6) | ng/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of high sensitivity c-Reactive Protein (Hs-CRP) | mg/L | screening, 3 months, 6 months, 9 months, 12 months | 
| Measurement of lipopolysaccharides (LPS) activity using the Limulus Amebocyte Lysate (LAL) assay | measured in endotoxin units (EU)/ml | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of glutaredoxin 1 (GRX-1) |  | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of Oxidized LDL |  | screening, 3 months, 6 months, 9 months, 12 months | 
| Total Antioxidant Capacity (TAC) |  | screening, 3 months, 6 months, 9 months, 12 months | 
| Concentration of reactive oxygen species (ROS) |  | screening, 3 months, 6 months, 9 months, 12 months | 
| Plasma metabolites assessed by untargeted liquid chromatography - mass spectrometry (LC-MS) metabolomics |  | screening, 3 months, 6 months, 9 months, 12 months | 
| Score from the Short Form 36 (SF-36) questionnaire | The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health.The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | screening, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 
| Score from the Well-being Questionnaire-12 (WBQ-12) | This questionnaire is designed to measure general well-being, including negative well-being, energy and positive well-being. The negative well-being scale score (range 0-12) is reversed and then summed with the Energy score (range 0-12) and Positive score (range 0-12) to produce a general well-being score (range 0-36). The higher the score the greater the sense of general well-being. | screening, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 
| Score from the Diabetes Treatment Satisfaction Questionnaire (DTSQ) | The DTSQ has been developed to assess patient satisfaction with diabetes treatment. The questionnaire is composed of two different factors. The ﬁrst factor assesses treatment satisfaction and consists of six questions and the second factor consists of two questions, which assess the burden from hyper- and hypoglycemia. Treatment satisfaction is assessed as the sum of the scores of the six questions on the ﬁrst factor (total score 36), with a higher score indicating higher treatment satisfaction. | screening, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 
| Time taken to complete the Trail making test A+B | The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The time taken to complete the test is used as the primary performance metric, measured in seconds and or minutes. | screening, 3 weeks, 6 weeks, 3 months, 6 months, 9 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 1 diabetes, low carbohydrate diet, randomized trial, adults, insulin, metabolic control