Influence of Diabetic Neuropathy on Activation of Brown Adipose Tissue
Influence of Diabetic Neuropathy on Activation of Brown Adipose Tissue
Influence of diabetic neuropathy on cold induced brown adipose tissue in type 1 diabetic
 patients.
The prevalence of type 1 diabetes has been steadily increasing for about 20 years. Despite
 therapeutic progress, between 20 and 65% of people with diabetes develop diabetic neuropathy,
 resulting in increased morbidity and mortality.

 Diabetic neuropathy is not limited to sensitive pain in the lower limbs. It also affects the
 fibres of the autonomic nervous system (ANS), which results in systemic complications, often
 disabling (erectile dysfunction, dysidrosis, gastroparesis, orthostatism, etc.) and a
 probable alteration in the body's thermogenic capacities, although this possibility has not
 been studied in humans. In rodents, it is possible to activate induced thermogenesis via
 central stimulation of the ANS or to inactivate it, which promotes the development of obesity
 and greater insulin resistance. This knowledge is based on cellular and animal models that
 have identified the bio-molecular mechanisms that give brown adipose tissue (BAT) the ability
 to dissipate energy in the form of heat.

 Induced thermogenesis is mediated by decoupling proteins 1 (DCS-1) located on the
 mitochondrial inner membrane of the TAB. DCS-1 decouple oxidative phosphorylation from ATP
 production, dissipating the proton gradient. The activation of UCP1 is particularly
 influenced by the sympathetic system and more particularly by catecholamines which will bind
 to ß3 adrenergic receptors (Rß3). In humans, the persistence of active areas of TAB has
 recently been demonstrated by positron emission tomography (PET) imaging using a glucose
 analogue radiotracer, 18F-Fluoro-Deoxy-Glucose (18F-FDG), coupled with the scanner (CT).
 Recently, it has been shown that the use of 18F-FDG PET coupled with magnetic resonance (MRI)
 is equally effective in differentiating TAB from white fat tissue with less patient
 irradiation. The activity of the TAB is estimated using the measurement of SUV (standard
 uptake value) which represents the total glycolytic activity of the tissue and is also
 commonly referred to as the total metabolic volume. It has been shown in humans that TAB
 activity is inversely correlated with body mass index and age and positively correlated with
 exposure to cold and stress levels[6]. Among diabetics, the data are disparate but the
 spontaneous prevalence of TAB appears to be reduced compared to the general population (1.1%
 vs 7.5%). To date, no studies have investigated a possible link between the decrease in TAB
 activity observed in diabetics and the presence of autonomic neuropathy, which is a common
 and often under-diagnosed complication of diabetes.

 The main purpose of this study is to evaluate whether the activity and distribution of TAB in
 patients with diabetes is influenced by the presence of diabetic neuropathy. On the other
 hand, if the existence of diabetic neuropathy influences energy expenditure in the event of
 exposure to cold. Finally, whether any differences in the activity and distribution of TAB
 could be related to changes in the central nervous system.

 The investigators plan to include a total of 24 patients with type 1 diabetes and separate
 them into 2 groups: group A; no neuropathic complications and group B; presence of
 neuropathy. All patients will be characterized in terms of clinical, metabolic and energy
 expenditure. The activity of the TAB will be evaluated through the use of 18F-FDG PET/IRM
 imaging, after a cold stimulation protocol (refrigerated jacket) in order to activate the TAB
 in a homogeneous manner among the participants.
Inclusion Criteria:

 1. Type 1 diabetes

 2. Patients who can understand the issue of this study and who are able to decide for
 themselves whether or not to participate in the study.

 3. Adult patient (>18 years old)

 4. Informed Consent form signed

 5. Differentiated inclusion:

 -  Group A: absence of neuropathy

 -  Group B: significant neuropathy

 Exclusion Criteria:

 1. Treatment with beta-blockers

 2. Alcohol consumption(> 50 gr/week)

 3. Allergy to 18F-FDG

 4. Participation in another clinical study (4 weeks prior to entry) that may influence
 the activity of brown adipose tissue

 5. Pregnancy

 6. Exposure to ionizing radiation greater than or equal to 5 mSv during the year
 preceding the PET-RMI planned in the study