Diabetes, Type 1 Diabetes
Conditions
Keywords
artificial pancreas, hybrid closed-loop, low carbohydrate diet, glucose control
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.
Interventions
OTHERLow carbohydrate diet
The study intervention will be an eucaloric low carbohydrate diet (15-20 % of carbohydrates) for 2 weeks.
OTHERbalanced diet
The control intervention will be a energy-matched balanced diet (50 % of carbohydrates) for 2 weeks.
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
| 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). |
| Mean glucose levels (mmol/l) | 2 weeks | Mean sensor glucose levels 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 |
| Daily manual bolus Insulin dose (U) | 2 weeks | Daily manual bolus insulin dose will be recorded by the insulin pump |
| 2 hour postprandial glucose increment (mmol/) | 2 weeks | 2 hour postprandial glucose increment 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). |
| Within day coefficient of variation of glucose (%) | 2 weeks | Within day coefficient of variation of glucose 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 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). |
| 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). |
| 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 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). |
| 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). |
| 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). |
| Change from baseline in lipid profile | 2 weeks | Plasma Lipid profile (total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides) |
| 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 |
| Change from baseline in fasting plasma metabolome | 2 weeks | Fasting serum sampling |
| 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 |
| 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). |
Countries
Switzerland
Outcome results
None listed