Effect of Insulin Detemir on Use of Energy in Type 1 Diabetes

• Total Energy Expenditure, Double-labelled Water Method [ Time Frame: Weeks 14-16, weeks 30-32 ] [ Designated as safety issue: No ]
  Total energy expenditure (TEE) measured after each treatment period by the double-labelled water (DLW) method. This technique required subjects to label their body water using oral administration of water labelled with 2 stable isotopes (2H218O). The clearance of 2H and 18O was measured over a two week period with daily collections of urine. The difference between the clearance of 2H and 18O is a measure of CO2 production rate. This can be converted to provide a measure of energy expenditure.
  
  
• Total Energy Expenditure, Dietary Record Method [ Time Frame: Weeks 14-16, weeks 30-32 ] [ Designated as safety issue: No ]
  The total energy expenditure (TEE) measured after each treatment period by the dietary record method. The calculation of energy balance is accomplished by compiling an accurate record of food intake over a period of time and measuring any changes in body weight that occur during that time. Data from the 7-day food diary was used to calculate TEE.
  
  

• Component of Total Energy Expenditure: Resting Energy Expenditure (REE) [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
  Resting energy expenditure (REE) is a component of TEE (total energy expenditure). It was measured at 2 different timepoints during the trial using indirect calorimetry (measurement of O2 consumption/CO2 production) after an overnight fast when subjects would be metabolising a mixture of carbohydrate and free fatty acid. This technique allowed the calculation of the rate of carbohydrate and lipid oxidation.
  
  
• Component of Total Energy Expenditure: Diet Induced Thermogenesis (DIT) [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
  Diet induced thermogenesis (DIT) is a component of TEE (total energy expenditure) and is the energy expenditure following feeding for anabolic processes. Subjects fasted overnight and rested for 1 hour. Multiple measurements of REE (resting energy expenditure) were taken. A fixed 600 kcal liquid meal was given and REE was measured over the next 3 hours. DIT was calculated as area under the curve of total REE-resting REE for the 3-hour period and was then converted to a per day measurement by taking into account each individual's average daily food intake.
  
  
• Component of Total Energy Expenditure: Physical Activity Thermogenesis [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
  Physical activity thermogenesis is a component of TEE (total energy expenditure). Subjects were asked not to change their physical activity levels. Physical activity thermogenesis can be calculated as the difference between TEE minus (REE + DIT), as long as volitional exercise is unchanged. Volitional exercise was assessed using Actiheart 3-D monitor readings. Subjects were asked to measure their normal activity for between 1 and 5 days prior to their visits at week 16 and week 32).
  
  
• Component of Total Energy Expenditure: Non-exercise Activity Thermogenesis (NEAT) [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
  Non-exercise activity thermogenesis is a component of TEE (total energy expenditure). Thermic efficiency was assessed by measuring O2 consumption/CO2 production while the subject exercised on a bike for 20 minutes while hooked up to a device that recorded their respiration (visit in week 14 and week 30). If thermic efficiency was unchanged and volitional exercise was unchanged, then any change in physical activity thermogenesis was due to changes in NEAT.
  
  
• Body Weight [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
  Body weight after each treatment period.
  
  
• Lean Body Mass [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
  Lean body mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
  
  
• Fat Mass [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
  Fat mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
  
  
• Waist:Hip Ratio [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
  At each time-point, 3 measurements each of waist and hip circumference were taken, then an average across the three measurements was calculated for both and the ratio was calculated as the waist average in cm divided by hip average in cm, and multiplied by 100.
  
  
• Hormonal Assessment: Adiponectin [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
  Adiponectin levels after each treatment period.
  
  
• Hormonal Assessment: Insulin-like Growth Factor-1 [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
  Insulin-like growth factor-1 (IGF-1) levels after each treatment period.
  
  
• Hormonal Assessment: Resistin [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
  Resistin levels after each treatment period.
  
  
• Hormonal Assessment: Leptin [ Time Frame: Week 14, week 30 ] [ Designated as safety issue: No ]
  Leptin levels after each treatment period.
  
  
• Glycosylated Haemoglobin A1c (HbA1c) [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
  Glycosylated haemoglobin A1c (HbA1c) after each treatment period.
  
  
• Fasting Plasma Glucose [ Time Frame: Week 16, week 32 ] [ Designated as safety issue: No ]
  Fasting plasma glucose (FPG) after each treatment period.
  
  
• Hypoglycaemic Episodes [ Time Frame: Weeks 0-32 ] [ Designated as safety issue: Yes ]
  Total number of hypoglycaemic episodes experienced in the study.
  
  
• Hypoglycaemic Episodes, Diurnal/Nocturnal [ Time Frame: Weeks 0-32 ] [ Designated as safety issue: Yes ]
  Total number of hypoglycaemic episodes during the day (diurnal) and the night (nocturnal) experienced in the study.
  
  

The study had been temporarily halted due to an unplanned interim analysis. The Sponsor is now aware that a further interim analysis has been performed by the site and therefore a decision has been made not to recommence the study