Carnitine Supplementation in Type 2 Diabetic Patients
Condition: Glucose Intolerance
MeSH terms: Glucose Intolerance
Study type: Interventional

Summary: 
      the results from animal studies and preliminary human studies show that carnitine
      availability and acetylcarnitine concentrations are low in insulin resistant states such as
      with type 2 diabetes mellitus. However, in humans, carnitine supplementation is sometimes
      beneficial, but not in everyone. We hypothesize that this variability in response might be
      due to differences between individuals in the amount of carnitine in the muscle i.e. subjects
      with a low initial carnitine status will benefit more from supplementation. The state of the
      art non-invasive magnetic resonance spectroscopy method allows us to identify patients muscle
      acetylcarnitine status. Here we aim to test whether carnitine improves insulin sensitivity,
      furthermore, whether acetylcarnitine concentration at baseline or other characteristics are
      associated with the response (in insulin sensitivity) to carnitine supplementation.
      Furthermore, we will examine the potentially positive effect of carnitine supplementation in
      type 2 diabetes patients on intrahepatic lipid content, acetylcarnitine formation, blood
      plasma metabolites, body composition, physical performance and quality of life
    

Detailed description: 
      Rationale: Type 2 diabetic patients are characterized by a decreased metabolic flexibility: a
      reduced capability to switch from fat oxidation in the basal state to carbohydrate oxidation
      in the insulin-stimulated state. This metabolic inflexibility is an early hallmark in the
      development of diabetes. Recent evidence suggests that a low carnitine availability may limit
      acetylcarnitine formation, thereby reducing metabolic flexibility. Thus, when substrate flux
      in the muscle is high, acetyl-CoA concentrations increase, leading to inhibition of pyruvate
      dehydrogenase (PDH) and thereby reducing glucose oxidation. The conversion of acetyl-CoA to
      acetylcarnitine relieves this acetyl-CoA pressure on PDH. In humans, carnitine
      supplementation is sometimes also beneficial, but not in everyone. Here we aim to test
      whether carnitine improves insulin sensitivity, furthermore, whether acetylcarnitine
      concentration at baseline or other characteristics are associated with the response (in
      insulin sensitivity) to carnitine supplementation. Furthermore, we will examine the
      potentially positive effect of carnitine supplementation in type 2 diabetes patients on
      intrahepatic lipid content, acetylcarnitine formation, blood plasma metabolites, body
      composition, physical performance and quality of life Objective: The primary objective is to
      investigate whether carnitine improves insulin sensitivity, furthermore, whether
      acetylcarnitine concentration at baseline or other characteristics are associated with the
      response (in insulin sensitivity) to carnitine supplementation. Furthermore, we will examine
      the potentially positive effect of carnitine supplementation in type 2 diabetes patients on
      intrahepatic lipid content, acetylcarnitine formation, blood plasma metabolites, body
      composition, physical performance and quality of life Study design: The current study is an
      interventional design with one study arm. Subjects will not be blinded for the intervention
      since all subjects will receive oral carnitine supplementation.

      Study population: n=32, patient with type 2 diabetes (BMI 25-38, age 40-75 years) male and
      female will be included. Only subjects with relatively well-controlled non-insulin depended
      diabetes will be included.

      Intervention (if applicable): Participants will be asked to take three chewing tablets of
      L-carnitine (330mg), three times a day (breakfast, lunch and dinner), for 96 days.

      Main study parameters/endpoints: The primary study endpoints are insulin sensitivity and
      metabolic flexibility, measured by the hyperinsulinemic-euglycemic clamp. Secondary endpoints
      are maximal acetylcarnitine concentrations after exercise, Intrahepatic lipid content, body
      composition, metabolites in the blood before (i.e. glucose, free fatty acids, triglycerides,
      cholesterol, insulin), functional markers of physical performance, cognition, quality of life
      and quality of sleep.
    

Intervention name(s): Carnitene (L-Carnitine or Levocarnitine)
Intervention type(s): Drug
Intervention description(s): All subjects will undergo oral Carnitene (L-Carnitine or levocarnitine) supplementation for 96 days.The total dosage of L-carnitine per day will be 2970mg. Consumption of the chewing tablets will be divided over the day. Intake of these chewing tablets will be during breakfast (990mg), lunch (990mg) and during diner (990mg). Since the chewing tablets are only available in concentrations of 330mg, participants have to consume 3 chewing tablets per meal, a total of 9 chewing tablets each day.
Intervention model: Single Group Assignment
Intervention model description: One group with type 2 diabetic patients who will undergo oral L-carnitine supplementation for 96 days
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Insulin sensitivity; Metabolic flexibility