Glucose-dependent Asprosin Dynamics
Condition: Diabetes Mellitus
MeSH terms: Marfan Syndrome
Study type: Observational

Summary: 
      The study entitled " Asprosin Dynamics relating to serum Glucose levels under controlled
      alterations" investigates the dynamics of Asprosin in relation to glucose levels under
      controlled conditions in diabetic patients.
    

Detailed description: 
      The Pilot study entitled Asprosin Dynamics relating to serum Glucose levels under controlled
      alterations is designed to date the asprosin kinetics at various metabolic states relating to
      serum glucose and the correlation between asprosin and the known glucose regulating hormones.
      Asprosin is the C-terminal cleavage product of profibrilln. This new hormone is encoded by
      FBN1 Gen (Amino acid residues 2732 to 2871, molecular weight 30 kDa), which also encodes
      fibrillin. The hormone was initially discovered during the analysis of the genome of patients
      with the extremely rare Wiedemann Rautenstrauch syndrome. According to the data so far,
      asprosin is a fast induced protein hormone that acts on the liver through cell membrane
      receptors, where it activates the G protein cAMP PKA pathway, leading to a rapid release of
      glucose into the circulation and to compensatory insulin production. The above seems to match
      the constellation found in overweight type 2 diabetes patients or patients with metabolic
      syndrome (insulin resistance). Diabetic mice were able to normalize their glucose and insulin
      levels by asprosin-binding antibodies. According to a recent study, asprosin had no influence
      on the serum concentration of glucagon, epinephrine, norepinephrine and cortisol in mice. In
      humans it is known that asprosin increases during fasting.

      The liver related glucose release into the blood circulation is crucial for the brain
      function and overall survival during fasting. In addition, a compensatory rise in asprosin is
      expected during a hypoglycemic episode. In this pilot study, the asprosin concentration is
      measured both in participants with type 1 Diabetes mellitus, with or without hypoglycemia
      unawareness during a hypoglycemic phase. These relevant measurements are compared in the two
      subgroups, consisting of 5 persons each. By correlating asprosin values with other regulating
      hormones, there is hope to better understand the pathomechanism of hypoglycemia unawareness.
      Recently discovered is that the recombinant asprosin administration in mice allows both the
      blood glucose and the insulin to rise. It is therefore very likely that further studying of
      asprosin could provide new insights into the (patho) physiology of the intermediary
      metabolism disorder.

      According to the above, the following hypotheses arise:

      Asprosin dynamics relating to serum Glucose levels under controlled alteration:

      Asprosin, as fast induced protein hormone, increases serum levels in type 1 diabetics with or
      without diabetes late complications during a hypoglycemic phase. Asprosin increases serum
      levels more significantly in diabetics without hypoglycemia unawareness compared to diabetics
      with hypoglycemia unawareness. There is probably no correlation between asprosin and the
      previous known regulating hormones. In order to investigate these hypotheses, study
      participants will be initially profoundly examined in our Clinical Study Center regarding
      both their glycemic metabolical responses and the clinical findings relating to their
      possible micro- and macrovascular complications. In addition to this quality of life, well
      being, depression and neuropathic pain is going to be taken into account. This is to be the
      first study of its kind, in which plasma levels of asprosin is determined and Type 1
      diabetics with and without hypoglycemia unawareness are thoroughly examined in order to
      identify possible differences and similarities for the better determination of the new
      hormone utilizing the framework of hyperinsulinemic Clamp Tests. The intention behind is to
      better understand the (patho) physiology of the hypoglycaemia unawareness, as well as to
      better characterize the physiological properties of asprosin
    

Intervention name(s): Clamp study
Intervention type(s): Diagnostic Test
Intervention description(s): Clamp study to achieve high, normal, and lower glucose levels to study the dynamics of Asprosin.
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        10 diabetic patients, five with and five without impairment in hypoglycemia awareness were
        included in the study.
      
Biospecimen description: 
      Biobank, including serum and EDTA plasma.