Glucose-dependent Asprosin Dynamics
- Conditions
- Diabetes Mellitus
- Interventions
- Diagnostic Test: Clamp study
- Registration Number
- NCT03358121
- Lead Sponsor
- Heidelberg University
- Brief 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Diabetics with hypoglycemia awareness Clamp study Diabetic patients with impaired hypoglycemia awareness. No interventions were performed, the study is purely observational. Diabetics without hypoglycemia awareness Clamp study Diabetic patients without impaired hypoglycemia awareness. No interventions were performed, the study is purely observational.
- Primary Outcome Measures
Name Time Method Asprosin dynamics during clamp study, five hours Euglycemic hyperinsulinemic clamp It is a scientific test for the determination tissue sensitivity to insulin. The asprosin kinetic in various hyperglycemic and euglycemic phases as well as the correlation between asprosin levels to the other known regulating hormones will be investigated.
An intravenous glucose tolerance test takes place in the morning and the serum glucose is controlled. Afterwards glucose 20 percent and insulin solution normal insulin is infused in order to set serum glucose manually at a target value of 90 mg per dl. The same test is performed with a glucose serum level of about 60 mg per dl, corresponding to physiological fasting serum glucose values. This is done in order to be able to assess asprosin kinetics even at lower serum glucose levels. At the end of this last hour, blood tests for the hormone measurement are performed. The duration of the examination is approximately 5 hours. Measurement of Asprosin is analyzed by ELISA
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Medizinische Klinik, University Hospital
🇩🇪Heidelberg, Baden-Wuerttemberg, Germany