Looping Whilst Restricting Carbohydrates
- Conditions
- DiabetesType 1 Diabetes
- Interventions
- Other: Low carbohydrate dietOther: balanced diet
- Registration Number
- NCT03932630
- Lead Sponsor
- Insel Gruppe AG, University Hospital Bern
- Brief Summary
To investigate the efficacy, safety and utility of hybrid closed-loop glucose control during a low carbohydrate vs. iso-energetic balanced diet in individuals with type 1 diabetes.
- Detailed Description
Closed-loop systems combining an insulin pump, a glucose sensor and a dosing algorithm that adjusts insulin delivery in a glucose-responsive manner achieve significantly better glucose control than conventional therapy in type 1 diabetes. Achieving satisfactory postprandial glucose control, however, continues to be challenging. The main limitation is the delayed pharmacokinetics and -dynamics of subcutaneously administered insulin with peak actions between 1 and 2 hours. Conversely, glucose levels typically rise within 10minutes following carbohydrate intake. This mismatch largely explains the inability of current closed-loop systems to control postprandial glucose excursions and the increased risk of late postprandial hypoglycaemia in response to both user-derived meal bolus administration and reactive algorithm-driven insulin infusion.
Restricting carbohydrate may therefore significantly improve post-prandial glucose control whilst reducing hypoglycaemia. The efficacy of hybrid closed-loop operation in individuals with type 1 diabetes adhering to a low carbohydrate compared to a iso-caloric balanced diet has not been investigated to date.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Female and male subjects aged 18 years or older
- Diabetes mellitus Type 1 as definded by WHO for at least 2 years or C-peptide negative (<100 pmol/L with concomitant blood glucose > 4 mmol/L)
- hybrid-closed-loop Insulin therapy (Minimed 670G) for at least 2 months
- HbA1c <= 9 %
- The subject is willing and capable of adhering to the diet plan.
- Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator.
- Excess alcohol consumption (> 3 units/day for men, > 2 units/day for women)
- Pregnancy, planned pregnancy or breast feeding
- Current participation in another clinical trial
- Total daily insulin dose >2 IU/kg/day
- Nephrolithiasis
- Hereditary dyslipidemia
- Liver steatosis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Study intervention Low carbohydrate diet - Control intervention balanced diet -
- Primary Outcome Measures
Name Time Method Percentage of time in target glucose range (3.9 - 10.0 mmol/L) 2 weeks The percentage of time in target glucose range will be assessed using continuous glucose monitoring (CGM).
- Secondary Outcome Measures
Name Time Method Hypoglycemia burden quantified as the area under the curve (AUC) with glucose < 3 mmol/L 2 weeks Hypoglycemia burden will be assessed using continuous glucose monitoring (CGM).
Daily manual bolus Insulin dose (U) 2 weeks Daily manual bolus insulin dose will be recorded by the insulin pump
Percentage of time above target (>10 mmol/L) 2 weeks The percentage of time below target (\>10 mmol/L) will be assessed using continuous glucose monitoring (CGM).
Percentage of time in hypoglycemia (<3.0 mmol/L) 2 weeks The percentage of time in hypoglycemia (\<3.0 mmol/L) will be assessed using continuous glucose monitoring (CGM).
2 hour postprandial glucose increment (mmol/) 2 weeks 2 hour postprandial glucose increment will be assessed using continuous glucose monitoring (CGM).
Between days coefficient of variation of glucose (%) 2 weeks Between days coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).
Night-time mean glucose levels Between 00:00-06:00 over 2 weeks Mean sensor glucose levels will be assessed using continuous glucose monitoring (CGM).
Within night-time standard deviation of glucose (mmol/l)compared to within daytime period (06: - 24:00) standard deviation of glucose (mmol/l) Between 00:00-06:00 over 2 weeks Standard deviation of glucose will be assessed using continuous glucose monitoring (CGM).
Percentage of time in hyperglycemia (>16.7 mmol/L) 2 weeks The percentage of time in hyperglycemia (\>16.7 mmol/L) will be assessed using continuous glucose monitoring (CGM).
Total daily insulin dose (U) 2 weeks Total daily insulin dose will be recorded by the insulin pump
Within day coefficient of variation of glucose (%) 2 weeks Within day coefficient of variation of glucose will be assessed using continuous glucose monitoring (CGM).
Percentage of time below target (<3.9 mmol/L) 2 weeks The percentage of time below target (\<3.9 mmol/L) will be assessed using continuous glucose monitoring (CGM).
Change from baseline in lipid profile 2 weeks Plasma Lipid profile (total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides)
Change from baseline in fasting plasma metabolome 2 weeks Fasting serum sampling
Mean glucose levels (mmol/l) 2 weeks Mean sensor glucose levels will be assessed using continuous glucose monitoring (CGM).
Within-day standard deviation of glucose (mmol/l) 2 weeks Within-day standard deviation of glucose will be assessed using continuous glucose monitoring (CGM).
Night-time percentage of time below target (< 3.9 mmol/L) Between 00:00-06:00 over 2 weeks Percentage of time below target will be assessed using continuous glucose monitoring (CGM).
Night-time percentage of time in hypoglycemia (< 3.0 mmol/L) Between 00:00-06:00 over 2 weeks Percentage of time in hypoglycemia will be assessed using continuous glucose monitoring (CGM).
Night-time percentage of time in target glucose range (3.9 - 10.0 mmol/L) Between 00:00-06:00 over 2 weeks Percentage of time in target glucose range will be assessed using continuous glucose monitoring (CGM).
Night-time percentage of time above target (> 10.0 mmol/L) Between 00:00-06:00 over 2 weeks Percentage of time above target will be assessed using continuous glucose monitoring (CGM).
Night-time percentage of time in hyperglycemia (> 16.7 mmol/L) Between 00:00-06:00 over 2 weeks Percentage of time in hyperglycemia will be assessed using continuous glucose monitoring (CGM).
Within nighttime coefficient of variation of glucose(%) Between 00:00-06:00 over 2 weeks Coefficient of variation of glucose (%) will be assessed using continuous glucose monitoring (CGM).
Total daily calorie intake (kcal/day) 2 weeks Total daily calorie intake will be assessed based on photo-documentation of dietary intake
Mean beta-hydroxy butyrate level 2 weeks based on download of blood Ketone meter
Incidence of (serious) adverse events 12 weeks Incidence of severe hypoglycaemia, signficant hyperglycaemia with ketonemia, other SAEs, adverse events, adverse defice effects and device deficiencies
Percentage of time when pump was in Auto-mode 2 weeks Based on pump data download
Trial Locations
- Locations (1)
University Department of Endocrinology, Diabetology, Clinical Nutrition and Metabolism
🇨ðŸ‡Bern, Switzerland